AbstractSynergistic chemo-photodynamic therapy has garnered attention in the field of cancer treatment. Here, a pH cascade-responsive micellar nanoplatform with nucleus-targeted ability, for effective synergistic chemo-photodynamic cancer treatment, was fabricated. In this micellar nanoplatform, 5-(4-carboxyphenyl)-10,15,20-triphenylporphyrin (Por), a photodynamic therapy (PDT) agent was utilized for carrying the novel anticancer drug GNA002 to construct a hydrophobic core, and cyclic RGD peptide (cRGD)-modified polyethylene glycol (PEG) (cRGD-PEG) connected the cell-penetrating peptide hexaarginine (R6) through a pH-responsive hydrazone bond (cRGD-PEG-N = CH-R6) to serve as a hydrophilic shell for increasing blood circulation time. After passively accumulating in tumor sites, the self-assembled GNA002-loaded nanoparticles were actively internalized into cancer cells via the cRGD ligands. Once phagocytosed by lysosomes, the acidity-triggered detachment of the cRGD-PEG shell led to the formation of R6-coated secondary nanoparticles and subsequent R6-mediated nucleus-targeted drug delivery. Combined with GNA002-induced nucleus-specific chemotherapy, reactive oxygen species produced by Por under 532-nm laser irradiation achieved a potent synergistic chemo-photodynamic cancer treatment. Moreover, our in vitro and in vivo anticancer investigations revealed high cancer-suppression efficacy of this ideal multifunctional nanoplatform, indicating that it could be a promising candidate for synergistic anticancer therapy.

01 Sep 2020·International Journal of PharmaceuticsQ2 · MEDICINE

In vitro/in vivo evaluation of pH-sensitive Gambogenic acid loaded Zein nanoparticles with polydopamine coating

Q2 · MEDICINE

Article

Author: Hong, Lufeng ; Liu, Huanhuan ; Dong, Qiannian ; Wang, Beilei ; Zhang, Caiyun ; Qian, Jiajia ; Zha, Liqiong ; Chen, Weidong

As one of the active pharmaceutical ingredients in Gamboge, Gambogenic acid (GNA) has shown diverse anti-tumor activities. To reduce the vascular irritation of GNA and improve its water solubility, tumor targeting, and bioavailability, GNA loaded Zein nanoparticles (GNA@Zein NPs) was further coated by polydopamine (PDA) to develop GNA@Zein-PDA NPs by anti-solvent precipitation and surface modification. The results showed that particle size and Zeta potential of GNA@Zein-PDA NPs were about 310 nm and -40.8 mV with core-shell morphology confirmed by TEM. GNA@Zein-PDA NPs increased the water solubility of GNA by more than 700 times and showed pH-sensitive release behavior in PBS with pH 6.86. In vitro cytotoxicity tests showed that GNA@Zein-PDA NPs had higher inhibitory activity on HepG2 cells than free GNA, and their IC₅₀ were 1.59 μg/mL and 9.89 μg/mL, respectively. Additionally, the hemolysis and vascular irritation assay showed that GNA@Zein-PDA NPs had good cytocompatibility and reduced the irritation of GNA to blood vessels. Moreover, the in vivo pharmacokinetic experiments exhibited that the C_max and AUC_0-t of GNA@Zein-PDA NPs were significantly improved approximately by 2.09-fold and 3.48-fold over that of GNA, respectively. In conclusion, GNA@Zein-PDA NPs solve many defects of GNA and provide a tumor-targeting drug delivery for GNA.

NanoscaleQ2 · MATERIALS SCIENCE

Nuclear-targeted nanocarriers based on pH-sensitive amphiphiles for enhanced GNA002 delivery and chemotherapy

Q2 · MATERIALS SCIENCE

Article

Author: Xu, Xing ; Wang, Xu ; Liang, Yan ; Chen, Wantao ; Zhao, Fen ; Li, Yan ; Wang, Miaochen ; Li, Fan ; Sun, Yong

An original pH-sensitive amphiphile that can provide a triple-stage targeted GNA002 delivery was fabricated to precisely deliver GNA002 from the injection site to the nucleus.

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Preclinical	CN	Shanghai Jiao Tong University School of Medicine	-

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