In this study, we designed and synthesized a novel peptide-drug conjugate (PDC-DOX2), in which two doxorubicin (DOX) molecules are covalently linked to a modified peptide with two carboxyl groups (Pep-AA). In neutral aqueous solution, PDC-DOX2 can self-assemble into stable spherical micelles due to hydrophilic-hydrophobic interactions. The sphere morphology can provide for the feasibility of intravenous injections of such peptide drug conjugates. PDC-DOX2 nanomicelles are stable spherical structures under neutral conditions, while they aggregate with decreased pH values. The pH value affected the assembly performance of PDC-DOX2 to a certain extent. With a decrease in pH (from a neutral to an acid environment), the morphology transforms from independent nanomicelles to slightly aggregated micelles and then to very aggregate micelles with diameters of nearly 3000 nm. The surfaces of PDC-DOX2 micelles were positively charged due to the lysine and arginine residues in the peptides. To avoid being engulfed by macrophages in plasma and prolong their blood circulation time, we further coated the positively charged micelles with a negatively charged natural polysaccharide shell, hyaluronic acid (HA), to form core-shell structure nanomedicine HA@PDC-DOX2. HA has various advantages, such as biodegradability, non-inflammatory, and non-immunogenicity. In addition, HA-coated nanomicelles allow for enhanced targeting in cancer therapy because HA can interact with overexpressed receptors in cancer cells, such as cluster determinant 44 (CD44), receptor for hyaluronic acid mediated motility (RHAMM) and intercellular adhesion molecule 1 (ICAM-1). Particularly, we found that the amount of HA influences the properties of HA@PDC-DOX2. The particle size of HA@PDC-DOX2 decreases with increasing HA content. The amount of HA can regulate the particle size, and HA@PDC-DOX2 become more stable in solution due to eliminating electrostatic repulsion of PDC-DOX2. The schematic mechanism of HA@PDC-DOX2 is shown in Scheme 1. First, PDC-DOX2 self-assembles into nanomicelles in neutral aqueous solution. Then, HA@PDC-DOX2 is constructed by negative HA shells and positively PDC-DOX2 cores. HA@PDC-DOX2 can deliver DOX into tumor sites via passive and active targeting effects. The core-shell structure HA@PDC-DOX2 nanomedicine showed better treatment effects on hepatocellular carcinoma, compared with PDC-DOX2 micelles and free DOX.

In this study, we designed and synthesized a novel peptide-drug conjugate (PDC-DOX2), in which two doxorubicin (DOX) molecules are covalently linked to a modified peptide with two carboxyl groups (Pep-AA). In neutral aqueous solution, PDC-DOX2 can self-assemble into stable spherical micelles due to hydrophilic-hydrophobic interactions. The sphere morphology can provide for the feasibility of intravenous injections of such peptide drug conjugates. PDC-DOX2 nanomicelles are stable spherical structures under neutral conditions, while they aggregate with decreased pH values. The pH value affected the assembly performance of PDC-DOX2 to a certain extent. With a decrease in pH (from a neutral to an acid environment), the morphology transforms from independent nanomicelles to slightly aggregated micelles and then to very aggregate micelles with diameters of nearly 3000 nm. The surfaces of PDC-DOX2 micelles were positively charged due to the lysine and arginine residues in the peptides. To avoid being engulfed by macrophages in plasma and prolong their blood circulation time, we further coated the positively charged micelles with a negatively charged natural polysaccharide shell, hyaluronic acid (HA), to form core-shell structure nanomedicine HA@PDC-DOX2. HA has various advantages, such as biodegradability, non-inflammatory, and non-immunogenicity. In addition, HA-coated nanomicelles allow for enhanced targeting in cancer therapy because HA can interact with overexpressed receptors in cancer cells, such as cluster determinant 44 (CD44), receptor for hyaluronic acid mediated motility (RHAMM) and intercellular adhesion molecule 1 (ICAM-1). Particularly, we found that the amount of HA influences the properties of HA@PDC-DOX2. The particle size of HA@PDC-DOX2 decreases with increasing HA content. The amount of HA can regulate the particle size, and HA@PDC-DOX2 become more stable in solution due to eliminating electrostatic repulsion of PDC-DOX2. The schematic mechanism of HA@PDC-DOX2 is shown in Scheme 1. First, PDC-DOX2 self-assembles into nanomicelles in neutral aqueous solution. Then, HA@PDC-DOX2 is constructed by negative HA shells and positively PDC-DOX2 cores. HA@PDC-DOX2 can deliver DOX into tumor sites via passive and active targeting effects. The core-shell structure HA@PDC-DOX2 nanomedicine showed better treatment effects on hepatocellular carcinoma, compared with PDC-DOX2 micelles and free DOX.

In this study, we designed and synthesized a novel peptide-drug conjugate (PDC-DOX2), in which two doxorubicin (DOX) molecules are covalently linked to a modified peptide with two carboxyl groups (Pep-AA). In neutral aqueous solution, PDC-DOX2 can self-assemble into stable spherical micelles due to hydrophilic-hydrophobic interactions. The sphere morphology can provide for the feasibility of intravenous injections of such peptide drug conjugates. PDC-DOX2 nanomicelles are stable spherical structures under neutral conditions, while they aggregate with decreased pH values. The pH value affected the assembly performance of PDC-DOX2 to a certain extent. With a decrease in pH (from a neutral to an acid environment), the morphology transforms from independent nanomicelles to slightly aggregated micelles and then to very aggregate micelles with diameters of nearly 3000 nm. The surfaces of PDC-DOX2 micelles were positively charged due to the lysine and arginine residues in the peptides. To avoid being engulfed by macrophages in plasma and prolong their blood circulation time, we further coated the positively charged micelles with a negatively charged natural polysaccharide shell, hyaluronic acid (HA), to form core-shell structure nanomedicine HA@PDC-DOX2. HA has various advantages, such as biodegradability, non-inflammatory, and non-immunogenicity. In addition, HA-coated nanomicelles allow for enhanced targeting in cancer therapy because HA can interact with overexpressed receptors in cancer cells, such as cluster determinant 44 (CD44), receptor for hyaluronic acid mediated motility (RHAMM) and intercellular adhesion molecule 1 (ICAM-1). Particularly, we found that the amount of HA influences the properties of HA@PDC-DOX2. The particle size of HA@PDC-DOX2 decreases with increasing HA content. The amount of HA can regulate the particle size, and HA@PDC-DOX2 become more stable in solution due to eliminating electrostatic repulsion of PDC-DOX2. The schematic mechanism of HA@PDC-DOX2 is shown in Scheme 1. First, PDC-DOX2 self-assembles into nanomicelles in neutral aqueous solution. Then, HA@PDC-DOX2 is constructed by negative HA shells and positively PDC-DOX2 cores. HA@PDC-DOX2 can deliver DOX into tumor sites via passive and active targeting effects. The core-shell structure HA@PDC-DOX2 nanomedicine showed better treatment effects on hepatocellular carcinoma, compared with PDC-DOX2 micelles and free DOX.

In this study, we designed and synthesized a novel peptide-drug conjugate (PDC-DOX2), in which two doxorubicin (DOX) molecules are covalently linked to a modified peptide with two carboxyl groups (Pep-AA). In neutral aqueous solution, PDC-DOX2 can self-assemble into stable spherical micelles due to hydrophilic-hydrophobic interactions. The sphere morphology can provide for the feasibility of intravenous injections of such peptide drug conjugates. PDC-DOX2 nanomicelles are stable spherical structures under neutral conditions, while they aggregate with decreased pH values. The pH value affected the assembly performance of PDC-DOX2 to a certain extent. With a decrease in pH (from a neutral to an acid environment), the morphology transforms from independent nanomicelles to slightly aggregated micelles and then to very aggregate micelles with diameters of nearly 3000 nm. The surfaces of PDC-DOX2 micelles were positively charged due to the lysine and arginine residues in the peptides. To avoid being engulfed by macrophages in plasma and prolong their blood circulation time, we further coated the positively charged micelles with a negatively charged natural polysaccharide shell, hyaluronic acid (HA), to form core-shell structure nanomedicine HA@PDC-DOX2. HA has various advantages, such as biodegradability, non-inflammatory, and non-immunogenicity. In addition, HA-coated nanomicelles allow for enhanced targeting in cancer therapy because HA can interact with overexpressed receptors in cancer cells, such as cluster determinant 44 (CD44), receptor for hyaluronic acid mediated motility (RHAMM) and intercellular adhesion molecule 1 (ICAM-1). Particularly, we found that the amount of HA influences the properties of HA@PDC-DOX2. The particle size of HA@PDC-DOX2 decreases with increasing HA content. The amount of HA can regulate the particle size, and HA@PDC-DOX2 become more stable in solution due to eliminating electrostatic repulsion of PDC-DOX2. The schematic mechanism of HA@PDC-DOX2 is shown in Scheme 1. First, PDC-DOX2 self-assembles into nanomicelles in neutral aqueous solution. Then, HA@PDC-DOX2 is constructed by negative HA shells and positively PDC-DOX2 cores. HA@PDC-DOX2 can deliver DOX into tumor sites via passive and active targeting effects. The core-shell structure HA@PDC-DOX2 nanomedicine showed better treatment effects on hepatocellular carcinoma, compared with PDC-DOX2 micelles and free DOX.

In this study, we designed and synthesized a novel peptide-drug conjugate (PDC-DOX2), in which two doxorubicin (DOX) molecules are covalently linked to a modified peptide with two carboxyl groups (Pep-AA). In neutral aqueous solution, PDC-DOX2 can self-assemble into stable spherical micelles due to hydrophilic-hydrophobic interactions. The sphere morphology can provide for the feasibility of intravenous injections of such peptide drug conjugates. PDC-DOX2 nanomicelles are stable spherical structures under neutral conditions, while they aggregate with decreased pH values. The pH value affected the assembly performance of PDC-DOX2 to a certain extent. With a decrease in pH (from a neutral to an acid environment), the morphology transforms from independent nanomicelles to slightly aggregated micelles and then to very aggregate micelles with diameters of nearly 3000 nm. The surfaces of PDC-DOX2 micelles were positively charged due to the lysine and arginine residues in the peptides. To avoid being engulfed by macrophages in plasma and prolong their blood circulation time, we further coated the positively charged micelles with a negatively charged natural polysaccharide shell, hyaluronic acid (HA), to form core-shell structure nanomedicine HA@PDC-DOX2. HA has various advantages, such as biodegradability, non-inflammatory, and non-immunogenicity. In addition, HA-coated nanomicelles allow for enhanced targeting in cancer therapy because HA can interact with overexpressed receptors in cancer cells, such as cluster determinant 44 (CD44), receptor for hyaluronic acid mediated motility (RHAMM) and intercellular adhesion molecule 1 (ICAM-1). Particularly, we found that the amount of HA influences the properties of HA@PDC-DOX2. The particle size of HA@PDC-DOX2 decreases with increasing HA content. The amount of HA can regulate the particle size, and HA@PDC-DOX2 become more stable in solution due to eliminating electrostatic repulsion of PDC-DOX2. The schematic mechanism of HA@PDC-DOX2 is shown in Scheme 1. First, PDC-DOX2 self-assembles into nanomicelles in neutral aqueous solution. Then, HA@PDC-DOX2 is constructed by negative HA shells and positively PDC-DOX2 cores. HA@PDC-DOX2 can deliver DOX into tumor sites via passive and active targeting effects. The core-shell structure HA@PDC-DOX2 nanomedicine showed better treatment effects on hepatocellular carcinoma, compared with PDC-DOX2 micelles and free DOX.

In this study, we designed and synthesized a novel peptide-drug conjugate (PDC-DOX2), in which two doxorubicin (DOX) molecules are covalently linked to a modified peptide with two carboxyl groups (Pep-AA). In neutral aqueous solution, PDC-DOX2 can self-assemble into stable spherical micelles due to hydrophilic-hydrophobic interactions. The sphere morphology can provide for the feasibility of intravenous injections of such peptide drug conjugates. PDC-DOX2 nanomicelles are stable spherical structures under neutral conditions, while they aggregate with decreased pH values. The pH value affected the assembly performance of PDC-DOX2 to a certain extent. With a decrease in pH (from a neutral to an acid environment), the morphology transforms from independent nanomicelles to slightly aggregated micelles and then to very aggregate micelles with diameters of nearly 3000 nm. The surfaces of PDC-DOX2 micelles were positively charged due to the lysine and arginine residues in the peptides. To avoid being engulfed by macrophages in plasma and prolong their blood circulation time, we further coated the positively charged micelles with a negatively charged natural polysaccharide shell, hyaluronic acid (HA), to form core-shell structure nanomedicine HA@PDC-DOX2. HA has various advantages, such as biodegradability, non-inflammatory, and non-immunogenicity. In addition, HA-coated nanomicelles allow for enhanced targeting in cancer therapy because HA can interact with overexpressed receptors in cancer cells, such as cluster determinant 44 (CD44), receptor for hyaluronic acid mediated motility (RHAMM) and intercellular adhesion molecule 1 (ICAM-1). Particularly, we found that the amount of HA influences the properties of HA@PDC-DOX2. The particle size of HA@PDC-DOX2 decreases with increasing HA content. The amount of HA can regulate the particle size, and HA@PDC-DOX2 become more stable in solution due to eliminating electrostatic repulsion of PDC-DOX2. The schematic mechanism of HA@PDC-DOX2 is shown in Scheme 1. First, PDC-DOX2 self-assembles into nanomicelles in neutral aqueous solution. Then, HA@PDC-DOX2 is constructed by negative HA shells and positively PDC-DOX2 cores. HA@PDC-DOX2 can deliver DOX into tumor sites via passive and active targeting effects. The core-shell structure HA@PDC-DOX2 nanomedicine showed better treatment effects on hepatocellular carcinoma, compared with PDC-DOX2 micelles and free DOX.

In this study, we designed and synthesized a novel peptide-drug conjugate (PDC-DOX2), in which two doxorubicin (DOX) molecules are covalently linked to a modified peptide with two carboxyl groups (Pep-AA). In neutral aqueous solution, PDC-DOX2 can self-assemble into stable spherical micelles due to hydrophilic-hydrophobic interactions. The sphere morphology can provide for the feasibility of intravenous injections of such peptide drug conjugates. PDC-DOX2 nanomicelles are stable spherical structures under neutral conditions, while they aggregate with decreased pH values. The pH value affected the assembly performance of PDC-DOX2 to a certain extent. With a decrease in pH (from a neutral to an acid environment), the morphology transforms from independent nanomicelles to slightly aggregated micelles and then to very aggregate micelles with diameters of nearly 3000 nm. The surfaces of PDC-DOX2 micelles were positively charged due to the lysine and arginine residues in the peptides. To avoid being engulfed by macrophages in plasma and prolong their blood circulation time, we further coated the positively charged micelles with a negatively charged natural polysaccharide shell, hyaluronic acid (HA), to form core-shell structure nanomedicine HA@PDC-DOX2. HA has various advantages, such as biodegradability, non-inflammatory, and non-immunogenicity. In addition, HA-coated nanomicelles allow for enhanced targeting in cancer therapy because HA can interact with overexpressed receptors in cancer cells, such as cluster determinant 44 (CD44), receptor for hyaluronic acid mediated motility (RHAMM) and intercellular adhesion molecule 1 (ICAM-1). Particularly, we found that the amount of HA influences the properties of HA@PDC-DOX2. The particle size of HA@PDC-DOX2 decreases with increasing HA content. The amount of HA can regulate the particle size, and HA@PDC-DOX2 become more stable in solution due to eliminating electrostatic repulsion of PDC-DOX2. The schematic mechanism of HA@PDC-DOX2 is shown in Scheme 1. First, PDC-DOX2 self-assembles into nanomicelles in neutral aqueous solution. Then, HA@PDC-DOX2 is constructed by negative HA shells and positively PDC-DOX2 cores. HA@PDC-DOX2 can deliver DOX into tumor sites via passive and active targeting effects. The core-shell structure HA@PDC-DOX2 nanomedicine showed better treatment effects on hepatocellular carcinoma, compared with PDC-DOX2 micelles and free DOX.

In this study, we designed and synthesized a novel peptide-drug conjugate (PDC-DOX2), in which two doxorubicin (DOX) molecules are covalently linked to a modified peptide with two carboxyl groups (Pep-AA). In neutral aqueous solution, PDC-DOX2 can self-assemble into stable spherical micelles due to hydrophilic-hydrophobic interactions. The sphere morphology can provide for the feasibility of intravenous injections of such peptide drug conjugates. PDC-DOX2 nanomicelles are stable spherical structures under neutral conditions, while they aggregate with decreased pH values. The pH value affected the assembly performance of PDC-DOX2 to a certain extent. With a decrease in pH (from a neutral to an acid environment), the morphology transforms from independent nanomicelles to slightly aggregated micelles and then to very aggregate micelles with diameters of nearly 3000 nm. The surfaces of PDC-DOX2 micelles were positively charged due to the lysine and arginine residues in the peptides. To avoid being engulfed by macrophages in plasma and prolong their blood circulation time, we further coated the positively charged micelles with a negatively charged natural polysaccharide shell, hyaluronic acid (HA), to form core-shell structure nanomedicine HA@PDC-DOX2. HA has various advantages, such as biodegradability, non-inflammatory, and non-immunogenicity. In addition, HA-coated nanomicelles allow for enhanced targeting in cancer therapy because HA can interact with overexpressed receptors in cancer cells, such as cluster determinant 44 (CD44), receptor for hyaluronic acid mediated motility (RHAMM) and intercellular adhesion molecule 1 (ICAM-1). Particularly, we found that the amount of HA influences the properties of HA@PDC-DOX2. The particle size of HA@PDC-DOX2 decreases with increasing HA content. The amount of HA can regulate the particle size, and HA@PDC-DOX2 become more stable in solution due to eliminating electrostatic repulsion of PDC-DOX2. The schematic mechanism of HA@PDC-DOX2 is shown in Scheme 1. First, PDC-DOX2 self-assembles into nanomicelles in neutral aqueous solution. Then, HA@PDC-DOX2 is constructed by negative HA shells and positively PDC-DOX2 cores. HA@PDC-DOX2 can deliver DOX into tumor sites via passive and active targeting effects. The core-shell structure HA@PDC-DOX2 nanomedicine showed better treatment effects on hepatocellular carcinoma, compared with PDC-DOX2 micelles and free DOX.

In this study, we designed and synthesized a novel peptide-drug conjugate (PDC-DOX2), in which two doxorubicin (DOX) molecules are covalently linked to a modified peptide with two carboxyl groups (Pep-AA). In neutral aqueous solution, PDC-DOX2 can self-assemble into stable spherical micelles due to hydrophilic-hydrophobic interactions. The sphere morphology can provide for the feasibility of intravenous injections of such peptide drug conjugates. PDC-DOX2 nanomicelles are stable spherical structures under neutral conditions, while they aggregate with decreased pH values. The pH value affected the assembly performance of PDC-DOX2 to a certain extent. With a decrease in pH (from a neutral to an acid environment), the morphology transforms from independent nanomicelles to slightly aggregated micelles and then to very aggregate micelles with diameters of nearly 3000 nm. The surfaces of PDC-DOX2 micelles were positively charged due to the lysine and arginine residues in the peptides. To avoid being engulfed by macrophages in plasma and prolong their blood circulation time, we further coated the positively charged micelles with a negatively charged natural polysaccharide shell, hyaluronic acid (HA), to form core-shell structure nanomedicine HA@PDC-DOX2. HA has various advantages, such as biodegradability, non-inflammatory, and non-immunogenicity. In addition, HA-coated nanomicelles allow for enhanced targeting in cancer therapy because HA can interact with overexpressed receptors in cancer cells, such as cluster determinant 44 (CD44), receptor for hyaluronic acid mediated motility (RHAMM) and intercellular adhesion molecule 1 (ICAM-1). Particularly, we found that the amount of HA influences the properties of HA@PDC-DOX2. The particle size of HA@PDC-DOX2 decreases with increasing HA content. The amount of HA can regulate the particle size, and HA@PDC-DOX2 become more stable in solution due to eliminating electrostatic repulsion of PDC-DOX2. The schematic mechanism of HA@PDC-DOX2 is shown in Scheme 1. First, PDC-DOX2 self-assembles into nanomicelles in neutral aqueous solution. Then, HA@PDC-DOX2 is constructed by negative HA shells and positively PDC-DOX2 cores. HA@PDC-DOX2 can deliver DOX into tumor sites via passive and active targeting effects. The core-shell structure HA@PDC-DOX2 nanomedicine showed better treatment effects on hepatocellular carcinoma, compared with PDC-DOX2 micelles and free DOX.

In this study, we designed and synthesized a novel peptide-drug conjugate (PDC-DOX2), in which two doxorubicin (DOX) molecules are covalently linked to a modified peptide with two carboxyl groups (Pep-AA). In neutral aqueous solution, PDC-DOX2 can self-assemble into stable spherical micelles due to hydrophilic-hydrophobic interactions. The sphere morphology can provide for the feasibility of intravenous injections of such peptide drug conjugates. PDC-DOX2 nanomicelles are stable spherical structures under neutral conditions, while they aggregate with decreased pH values. The pH value affected the assembly performance of PDC-DOX2 to a certain extent. With a decrease in pH (from a neutral to an acid environment), the morphology transforms from independent nanomicelles to slightly aggregated micelles and then to very aggregate micelles with diameters of nearly 3000 nm. The surfaces of PDC-DOX2 micelles were positively charged due to the lysine and arginine residues in the peptides. To avoid being engulfed by macrophages in plasma and prolong their blood circulation time, we further coated the positively charged micelles with a negatively charged natural polysaccharide shell, hyaluronic acid (HA), to form core-shell structure nanomedicine HA@PDC-DOX2. HA has various advantages, such as biodegradability, non-inflammatory, and non-immunogenicity. In addition, HA-coated nanomicelles allow for enhanced targeting in cancer therapy because HA can interact with overexpressed receptors in cancer cells, such as cluster determinant 44 (CD44), receptor for hyaluronic acid mediated motility (RHAMM) and intercellular adhesion molecule 1 (ICAM-1). Particularly, we found that the amount of HA influences the properties of HA@PDC-DOX2. The particle size of HA@PDC-DOX2 decreases with increasing HA content. The amount of HA can regulate the particle size, and HA@PDC-DOX2 become more stable in solution due to eliminating electrostatic repulsion of PDC-DOX2. The schematic mechanism of HA@PDC-DOX2 is shown in Scheme 1. First, PDC-DOX2 self-assembles into nanomicelles in neutral aqueous solution. Then, HA@PDC-DOX2 is constructed by negative HA shells and positively PDC-DOX2 cores. HA@PDC-DOX2 can deliver DOX into tumor sites via passive and active targeting effects. The core-shell structure HA@PDC-DOX2 nanomedicine showed better treatment effects on hepatocellular carcinoma, compared with PDC-DOX2 micelles and free DOX.

In this study, we designed and synthesized a novel peptide-drug conjugate (PDC-DOX2), in which two doxorubicin (DOX) molecules are covalently linked to a modified peptide with two carboxyl groups (Pep-AA). In neutral aqueous solution, PDC-DOX2 can self-assemble into stable spherical micelles due to hydrophilic-hydrophobic interactions. The sphere morphology can provide for the feasibility of intravenous injections of such peptide drug conjugates. PDC-DOX2 nanomicelles are stable spherical structures under neutral conditions, while they aggregate with decreased pH values. The pH value affected the assembly performance of PDC-DOX2 to a certain extent. With a decrease in pH (from a neutral to an acid environment), the morphology transforms from independent nanomicelles to slightly aggregated micelles and then to very aggregate micelles with diameters of nearly 3000 nm. The surfaces of PDC-DOX2 micelles were positively charged due to the lysine and arginine residues in the peptides. To avoid being engulfed by macrophages in plasma and prolong their blood circulation time, we further coated the positively charged micelles with a negatively charged natural polysaccharide shell, hyaluronic acid (HA), to form core-shell structure nanomedicine HA@PDC-DOX2. HA has various advantages, such as biodegradability, non-inflammatory, and non-immunogenicity. In addition, HA-coated nanomicelles allow for enhanced targeting in cancer therapy because HA can interact with overexpressed receptors in cancer cells, such as cluster determinant 44 (CD44), receptor for hyaluronic acid mediated motility (RHAMM) and intercellular adhesion molecule 1 (ICAM-1). Particularly, we found that the amount of HA influences the properties of HA@PDC-DOX2. The particle size of HA@PDC-DOX2 decreases with increasing HA content. The amount of HA can regulate the particle size, and HA@PDC-DOX2 become more stable in solution due to eliminating electrostatic repulsion of PDC-DOX2. The schematic mechanism of HA@PDC-DOX2 is shown in Scheme 1. First, PDC-DOX2 self-assembles into nanomicelles in neutral aqueous solution. Then, HA@PDC-DOX2 is constructed by negative HA shells and positively PDC-DOX2 cores. HA@PDC-DOX2 can deliver DOX into tumor sites via passive and active targeting effects. The core-shell structure HA@PDC-DOX2 nanomedicine showed better treatment effects on hepatocellular carcinoma, compared with PDC-DOX2 micelles and free DOX.

In this study, we designed and synthesized a novel peptide-drug conjugate (PDC-DOX2), in which two doxorubicin (DOX) molecules are covalently linked to a modified peptide with two carboxyl groups (Pep-AA). In neutral aqueous solution, PDC-DOX2 can self-assemble into stable spherical micelles due to hydrophilic-hydrophobic interactions. The sphere morphology can provide for the feasibility of intravenous injections of such peptide drug conjugates. PDC-DOX2 nanomicelles are stable spherical structures under neutral conditions, while they aggregate with decreased pH values. The pH value affected the assembly performance of PDC-DOX2 to a certain extent. With a decrease in pH (from a neutral to an acid environment), the morphology transforms from independent nanomicelles to slightly aggregated micelles and then to very aggregate micelles with diameters of nearly 3000 nm. The surfaces of PDC-DOX2 micelles were positively charged due to the lysine and arginine residues in the peptides. To avoid being engulfed by macrophages in plasma and prolong their blood circulation time, we further coated the positively charged micelles with a negatively charged natural polysaccharide shell, hyaluronic acid (HA), to form core-shell structure nanomedicine HA@PDC-DOX2. HA has various advantages, such as biodegradability, non-inflammatory, and non-immunogenicity. In addition, HA-coated nanomicelles allow for enhanced targeting in cancer therapy because HA can interact with overexpressed receptors in cancer cells, such as cluster determinant 44 (CD44), receptor for hyaluronic acid mediated motility (RHAMM) and intercellular adhesion molecule 1 (ICAM-1). Particularly, we found that the amount of HA influences the properties of HA@PDC-DOX2. The particle size of HA@PDC-DOX2 decreases with increasing HA content. The amount of HA can regulate the particle size, and HA@PDC-DOX2 become more stable in solution due to eliminating electrostatic repulsion of PDC-DOX2. The schematic mechanism of HA@PDC-DOX2 is shown in Scheme 1. First, PDC-DOX2 self-assembles into nanomicelles in neutral aqueous solution. Then, HA@PDC-DOX2 is constructed by negative HA shells and positively PDC-DOX2 cores. HA@PDC-DOX2 can deliver DOX into tumor sites via passive and active targeting effects. The core-shell structure HA@PDC-DOX2 nanomedicine showed better treatment effects on hepatocellular carcinoma, compared with PDC-DOX2 micelles and free DOX.

In this study, we designed and synthesized a novel peptide-drug conjugate (PDC-DOX2), in which two doxorubicin (DOX) molecules are covalently linked to a modified peptide with two carboxyl groups (Pep-AA). In neutral aqueous solution, PDC-DOX2 can self-assemble into stable spherical micelles due to hydrophilic-hydrophobic interactions. The sphere morphology can provide for the feasibility of intravenous injections of such peptide drug conjugates. PDC-DOX2 nanomicelles are stable spherical structures under neutral conditions, while they aggregate with decreased pH values. The pH value affected the assembly performance of PDC-DOX2 to a certain extent. With a decrease in pH (from a neutral to an acid environment), the morphology transforms from independent nanomicelles to slightly aggregated micelles and then to very aggregate micelles with diameters of nearly 3000 nm. The surfaces of PDC-DOX2 micelles were positively charged due to the lysine and arginine residues in the peptides. To avoid being engulfed by macrophages in plasma and prolong their blood circulation time, we further coated the positively charged micelles with a negatively charged natural polysaccharide shell, hyaluronic acid (HA), to form core-shell structure nanomedicine HA@PDC-DOX2. HA has various advantages, such as biodegradability, non-inflammatory, and non-immunogenicity. In addition, HA-coated nanomicelles allow for enhanced targeting in cancer therapy because HA can interact with overexpressed receptors in cancer cells, such as cluster determinant 44 (CD44), receptor for hyaluronic acid mediated motility (RHAMM) and intercellular adhesion molecule 1 (ICAM-1). Particularly, we found that the amount of HA influences the properties of HA@PDC-DOX2. The particle size of HA@PDC-DOX2 decreases with increasing HA content. The amount of HA can regulate the particle size, and HA@PDC-DOX2 become more stable in solution due to eliminating electrostatic repulsion of PDC-DOX2. The schematic mechanism of HA@PDC-DOX2 is shown in Scheme 1. First, PDC-DOX2 self-assembles into nanomicelles in neutral aqueous solution. Then, HA@PDC-DOX2 is constructed by negative HA shells and positively PDC-DOX2 cores. HA@PDC-DOX2 can deliver DOX into tumor sites via passive and active targeting effects. The core-shell structure HA@PDC-DOX2 nanomedicine showed better treatment effects on hepatocellular carcinoma, compared with PDC-DOX2 micelles and free DOX.

In this study, we designed and synthesized a novel peptide-drug conjugate (PDC-DOX2), in which two doxorubicin (DOX) molecules are covalently linked to a modified peptide with two carboxyl groups (Pep-AA). In neutral aqueous solution, PDC-DOX2 can self-assemble into stable spherical micelles due to hydrophilic-hydrophobic interactions. The sphere morphology can provide for the feasibility of intravenous injections of such peptide drug conjugates. PDC-DOX2 nanomicelles are stable spherical structures under neutral conditions, while they aggregate with decreased pH values. The pH value affected the assembly performance of PDC-DOX2 to a certain extent. With a decrease in pH (from a neutral to an acid environment), the morphology transforms from independent nanomicelles to slightly aggregated micelles and then to very aggregate micelles with diameters of nearly 3000 nm. The surfaces of PDC-DOX2 micelles were positively charged due to the lysine and arginine residues in the peptides. To avoid being engulfed by macrophages in plasma and prolong their blood circulation time, we further coated the positively charged micelles with a negatively charged natural polysaccharide shell, hyaluronic acid (HA), to form core-shell structure nanomedicine HA@PDC-DOX2. HA has various advantages, such as biodegradability, non-inflammatory, and non-immunogenicity. In addition, HA-coated nanomicelles allow for enhanced targeting in cancer therapy because HA can interact with overexpressed receptors in cancer cells, such as cluster determinant 44 (CD44), receptor for hyaluronic acid mediated motility (RHAMM) and intercellular adhesion molecule 1 (ICAM-1). Particularly, we found that the amount of HA influences the properties of HA@PDC-DOX2. The particle size of HA@PDC-DOX2 decreases with increasing HA content. The amount of HA can regulate the particle size, and HA@PDC-DOX2 become more stable in solution due to eliminating electrostatic repulsion of PDC-DOX2. The schematic mechanism of HA@PDC-DOX2 is shown in Scheme 1. First, PDC-DOX2 self-assembles into nanomicelles in neutral aqueous solution. Then, HA@PDC-DOX2 is constructed by negative HA shells and positively PDC-DOX2 cores. HA@PDC-DOX2 can deliver DOX into tumor sites via passive and active targeting effects. The core-shell structure HA@PDC-DOX2 nanomedicine showed better treatment effects on hepatocellular carcinoma, compared with PDC-DOX2 micelles and free DOX.

In this study, we designed and synthesized a novel peptide-drug conjugate (PDC-DOX2), in which two doxorubicin (DOX) molecules are covalently linked to a modified peptide with two carboxyl groups (Pep-AA). In neutral aqueous solution, PDC-DOX2 can self-assemble into stable spherical micelles due to hydrophilic-hydrophobic interactions. The sphere morphology can provide for the feasibility of intravenous injections of such peptide drug conjugates. PDC-DOX2 nanomicelles are stable spherical structures under neutral conditions, while they aggregate with decreased pH values. The pH value affected the assembly performance of PDC-DOX2 to a certain extent. With a decrease in pH (from a neutral to an acid environment), the morphology transforms from independent nanomicelles to slightly aggregated micelles and then to very aggregate micelles with diameters of nearly 3000 nm. The surfaces of PDC-DOX2 micelles were positively charged due to the lysine and arginine residues in the peptides. To avoid being engulfed by macrophages in plasma and prolong their blood circulation time, we further coated the positively charged micelles with a negatively charged natural polysaccharide shell, hyaluronic acid (HA), to form core-shell structure nanomedicine HA@PDC-DOX2. HA has various advantages, such as biodegradability, non-inflammatory, and non-immunogenicity. In addition, HA-coated nanomicelles allow for enhanced targeting in cancer therapy because HA can interact with overexpressed receptors in cancer cells, such as cluster determinant 44 (CD44), receptor for hyaluronic acid mediated motility (RHAMM) and intercellular adhesion molecule 1 (ICAM-1). Particularly, we found that the amount of HA influences the properties of HA@PDC-DOX2. The particle size of HA@PDC-DOX2 decreases with increasing HA content. The amount of HA can regulate the particle size, and HA@PDC-DOX2 become more stable in solution due to eliminating electrostatic repulsion of PDC-DOX2. The schematic mechanism of HA@PDC-DOX2 is shown in Scheme 1. First, PDC-DOX2 self-assembles into nanomicelles in neutral aqueous solution. Then, HA@PDC-DOX2 is constructed by negative HA shells and positively PDC-DOX2 cores. HA@PDC-DOX2 can deliver DOX into tumor sites via passive and active targeting effects. The core-shell structure HA@PDC-DOX2 nanomedicine showed better treatment effects on hepatocellular carcinoma, compared with PDC-DOX2 micelles and free DOX.

In this study, we designed and synthesized a novel peptide-drug conjugate (PDC-DOX2), in which two doxorubicin (DOX) molecules are covalently linked to a modified peptide with two carboxyl groups (Pep-AA). In neutral aqueous solution, PDC-DOX2 can self-assemble into stable spherical micelles due to hydrophilic-hydrophobic interactions. The sphere morphology can provide for the feasibility of intravenous injections of such peptide drug conjugates. PDC-DOX2 nanomicelles are stable spherical structures under neutral conditions, while they aggregate with decreased pH values. The pH value affected the assembly performance of PDC-DOX2 to a certain extent. With a decrease in pH (from a neutral to an acid environment), the morphology transforms from independent nanomicelles to slightly aggregated micelles and then to very aggregate micelles with diameters of nearly 3000 nm. The surfaces of PDC-DOX2 micelles were positively charged due to the lysine and arginine residues in the peptides. To avoid being engulfed by macrophages in plasma and prolong their blood circulation time, we further coated the positively charged micelles with a negatively charged natural polysaccharide shell, hyaluronic acid (HA), to form core-shell structure nanomedicine HA@PDC-DOX2. HA has various advantages, such as biodegradability, non-inflammatory, and non-immunogenicity. In addition, HA-coated nanomicelles allow for enhanced targeting in cancer therapy because HA can interact with overexpressed receptors in cancer cells, such as cluster determinant 44 (CD44), receptor for hyaluronic acid mediated motility (RHAMM) and intercellular adhesion molecule 1 (ICAM-1). Particularly, we found that the amount of HA influences the properties of HA@PDC-DOX2. The particle size of HA@PDC-DOX2 decreases with increasing HA content. The amount of HA can regulate the particle size, and HA@PDC-DOX2 become more stable in solution due to eliminating electrostatic repulsion of PDC-DOX2. The schematic mechanism of HA@PDC-DOX2 is shown in Scheme 1. First, PDC-DOX2 self-assembles into nanomicelles in neutral aqueous solution. Then, HA@PDC-DOX2 is constructed by negative HA shells and positively PDC-DOX2 cores. HA@PDC-DOX2 can deliver DOX into tumor sites via passive and active targeting effects. The core-shell structure HA@PDC-DOX2 nanomedicine showed better treatment effects on hepatocellular carcinoma, compared with PDC-DOX2 micelles and free DOX.

In this study, we designed and synthesized a novel peptide-drug conjugate (PDC-DOX2), in which two doxorubicin (DOX) molecules are covalently linked to a modified peptide with two carboxyl groups (Pep-AA). In neutral aqueous solution, PDC-DOX2 can self-assemble into stable spherical micelles due to hydrophilic-hydrophobic interactions. The sphere morphology can provide for the feasibility of intravenous injections of such peptide drug conjugates. PDC-DOX2 nanomicelles are stable spherical structures under neutral conditions, while they aggregate with decreased pH values. The pH value affected the assembly performance of PDC-DOX2 to a certain extent. With a decrease in pH (from a neutral to an acid environment), the morphology transforms from independent nanomicelles to slightly aggregated micelles and then to very aggregate micelles with diameters of nearly 3000 nm. The surfaces of PDC-DOX2 micelles were positively charged due to the lysine and arginine residues in the peptides. To avoid being engulfed by macrophages in plasma and prolong their blood circulation time, we further coated the positively charged micelles with a negatively charged natural polysaccharide shell, hyaluronic acid (HA), to form core-shell structure nanomedicine HA@PDC-DOX2. HA has various advantages, such as biodegradability, non-inflammatory, and non-immunogenicity. In addition, HA-coated nanomicelles allow for enhanced targeting in cancer therapy because HA can interact with overexpressed receptors in cancer cells, such as cluster determinant 44 (CD44), receptor for hyaluronic acid mediated motility (RHAMM) and intercellular adhesion molecule 1 (ICAM-1). Particularly, we found that the amount of HA influences the properties of HA@PDC-DOX2. The particle size of HA@PDC-DOX2 decreases with increasing HA content. The amount of HA can regulate the particle size, and HA@PDC-DOX2 become more stable in solution due to eliminating electrostatic repulsion of PDC-DOX2. The schematic mechanism of HA@PDC-DOX2 is shown in Scheme 1. First, PDC-DOX2 self-assembles into nanomicelles in neutral aqueous solution. Then, HA@PDC-DOX2 is constructed by negative HA shells and positively PDC-DOX2 cores. HA@PDC-DOX2 can deliver DOX into tumor sites via passive and active targeting effects. The core-shell structure HA@PDC-DOX2 nanomedicine showed better treatment effects on hepatocellular carcinoma, compared with PDC-DOX2 micelles and free DOX.

In this study, we designed and synthesized a novel peptide-drug conjugate (PDC-DOX2), in which two doxorubicin (DOX) molecules are covalently linked to a modified peptide with two carboxyl groups (Pep-AA). In neutral aqueous solution, PDC-DOX2 can self-assemble into stable spherical micelles due to hydrophilic-hydrophobic interactions. The sphere morphology can provide for the feasibility of intravenous injections of such peptide drug conjugates. PDC-DOX2 nanomicelles are stable spherical structures under neutral conditions, while they aggregate with decreased pH values. The pH value affected the assembly performance of PDC-DOX2 to a certain extent. With a decrease in pH (from a neutral to an acid environment), the morphology transforms from independent nanomicelles to slightly aggregated micelles and then to very aggregate micelles with diameters of nearly 3000 nm. The surfaces of PDC-DOX2 micelles were positively charged due to the lysine and arginine residues in the peptides. To avoid being engulfed by macrophages in plasma and prolong their blood circulation time, we further coated the positively charged micelles with a negatively charged natural polysaccharide shell, hyaluronic acid (HA), to form core-shell structure nanomedicine HA@PDC-DOX2. HA has various advantages, such as biodegradability, non-inflammatory, and non-immunogenicity. In addition, HA-coated nanomicelles allow for enhanced targeting in cancer therapy because HA can interact with overexpressed receptors in cancer cells, such as cluster determinant 44 (CD44), receptor for hyaluronic acid mediated motility (RHAMM) and intercellular adhesion molecule 1 (ICAM-1). Particularly, we found that the amount of HA influences the properties of HA@PDC-DOX2. The particle size of HA@PDC-DOX2 decreases with increasing HA content. The amount of HA can regulate the particle size, and HA@PDC-DOX2 become more stable in solution due to eliminating electrostatic repulsion of PDC-DOX2. The schematic mechanism of HA@PDC-DOX2 is shown in Scheme 1. First, PDC-DOX2 self-assembles into nanomicelles in neutral aqueous solution. Then, HA@PDC-DOX2 is constructed by negative HA shells and positively PDC-DOX2 cores. HA@PDC-DOX2 can deliver DOX into tumor sites via passive and active targeting effects. The core-shell structure HA@PDC-DOX2 nanomedicine showed better treatment effects on hepatocellular carcinoma, compared with PDC-DOX2 micelles and free DOX.