In this study, prostate-specific membrane antigen (PSMA)-targeted and core-crosslinked micelles were developed based on prostate cancer-binding peptide (PCP) modified glycol chitosan-lipoic acid (PGC-LA) conjugate. The degree of substitution was 5.2 PCP groups and 10.7 lipoic acid groups per 100 sugar residues of glycol chitosan in PGC-LA copolymer. Docetaxel (DTX) was chosen as a model anti-tumor drug. The DTX-loaded micelles were prepared by an o/w method, and core-crosslinked micelles were further constructed by using a catalytic amount of dithiothreitol. The mean diameter of DTX-loaded core-crosslinked PGC-LA (DTX-PGC-LA/cc) micelles was 397 nm determined by dynamic light scattering (DLS). In vitro DTX released from core-crosslinked micelles was slower than that from non-crosslinked counterpart. Blank micelles exhibited good biocompatibility. Additionally, cellular uptake and cytotoxcity of PCP-modified micelles were higher than those of micelles without PCP in PSMA-positive LNCaP cells. Importantly, DTX-PGC-LA/cc demonstrated the stronger anti-tumor efficacy against LNCaP tumor xenograft models than DTX injection and other DTX-loaded micelles. Taken together, this study provides a potential way in developing actively targeted and core-crosslinked micelles for hydrophobic drug delivery in cancer therapy.
Wang Ruizhi,Zhou Guofeng,Yang Yuchan,Wang Shiqing,Gao Shanshan,Gao Dongmei,Wang Xiaolin
The advantages of deep tissue penetration and the high spatial accuracy of photothermal therapy have been widely studied. Gold, as a photothermal material, has received particular attention. Different sizes and shapes of gold have been studied and characterized for their varying photothermal
properties. The core–shell structure of gold nanoparticles and silica enhances the photothermal conversion through the coupling effect between gold clusters on the material’s surface. With excellent photothermal conversion performance, the core–shell nanoparticles can quickly
reach 40 °C in 200 s under the irradiation of 808 nm, 1.5 W·cm−2. The highest conversion temperature of these nanoparticles is 56 °C, and the photothermal conversion rate is 45%. In vitro cell experiments displayed that NPs with targeted function can
efficiently aggregate in prostate cancer cells and effectively kill cells. In vitro experiments showed that the tumor cells of mice after photothermal treatment completely disappeared after 15 days, which fully demonstrated the potential of the nanoparticles for targeted photothermal
therapy.
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