TPGS/hyaluronic acid dual-functionalized PLGA nanoparticles delivered through dissolving microneedles for markedly improved chemo-photothermal combined therapy of superficial tumor

• 作者: Tingting Peng Yao Huang Xiaoqian Feng Chune Zhu Shi Yin Xinyi Wang Xuequn Bai Xin Pan Chuanbin Wu
• 来源期刊: 药学学报（英文版）
• 年，卷（期）: 2021,（10）
• 所属期刊栏目: Original articles
• 页码范围: 3297-3309
• 页数: 13页
• 语种: 英文

摘要

Nanoparticles (NPs) have shown potential in cancer therapy,while a single administration conferring a satisfactory outcome is still unavailable.To address this issue,the dissolving microneedles(DMNs) were developed to locally deliver functionalized NPs with combined chemotherapy and photo-thermal therapy (PTT).α-Tocopheryl polyethylene glycol succinate (TPGS)/hyaluronic acid (HA) dual-functionalized PLGA NPs (HD10 NPs) were fabricated to co-load paclitaxel and indocyanine green.HD10 NPs significantly enhanced the cytotoxicity of low-dose paclitaxel because of active and mitochon-drial targeting by HA and TPGS,respectively.PTT could further sensitize tumor cells toward chemo-therapy by promoting apoptosis into the advanced period,highly activating caspase 3 enzyme,and significantly reducing the expression of survivin and MMP-9 proteins.Further,the anti-tumor effects of HD10 NPs delivered through different administration routes were conducted on the 4T1 tumor-bearing mice.After a single administration,HD10 NPs delivered with DMNs showed the best anti-tumor effect when giving chemotherapy alone.As expected,the anti-tumor effect was profoundly enhanced after combined therapy,and complete tumor ablation was achieved in the mice treated with DMNs and intra-tumor injection.Moreover,DMNs showed better safety due to moderate hyperthermia.Therefore,the DMNs along with combined chemo-photothermal therapy provide a viable treatment op-tion for superficial tumors.