Tumor-Homing and Penetrating Peptide-Functionalized Photosensitizer-Conjugated PEG-PLA Nanoparticles for Chemo-Photodynamic Combination Therapy of Drug-Resistant Cancer
Tumor-Homing and Penetrating Peptide-Functionalized Photosensitizer-Conjugated PEG-PLA Nanoparticles for Chemo-Photodynamic Combination Therapy of Drug-Resistant Cancer
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肿瘤归巢和穿透肽功能化光敏剂缀合 PEG-PLA 纳米颗粒用于耐药癌症的化学光动力联合治疗
DOI：
10.1021/acsami.6b04442
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发表时间：
2016-07-20
影响因子：
9.5
通讯作者：
Chen, Jun
中科院分区：
文献类型：
--
作者：
Feng, Xingye;Jiang, Di;Chen, Jun
光动力疗法（PDT）与化学疗法的结合在对抗耐药癌症方面具有巨大的潜力。然而，摆在我们面前的主要挑战是如何实现光敏剂和化学药物的高负载能力，以及如何有效地向耐药肿瘤输送药物。在本研究中，我们在合成PPa共轭两亲共聚物PPa- pla - peg - pla -PPa的基础上，制备了一种用于光敏剂（焦酚a， PPa）和化学药物（紫杉醇，PTX）共递送的纳米载体。得到的纳米颗粒（PP NP）对两种药物都具有令人满意的高载药量。为了实现有效的肿瘤靶向治疗，PP NP表面修饰了肿瘤归巢穿透肽F3。体外细胞实验表明，f3功能化的PP NP （F3-PP NP）比PP NP具有更高的细胞关联性，具有最强的抗增殖作用。此外，与未修饰的纳米颗粒相比，F3-PP NP在肿瘤部位表现出更优先的富集。体内药效学评价表明，与单纯化疗或单纯PDT治疗相比，PP NP（+激光）治疗荷瘤小鼠的生存时间更长。F3肽功能化后，联合治疗的抗肿瘤效果进一步提高。总之，这些结果表明，靶向联合治疗可能为耐药肿瘤的治疗铺平了一条有希望的道路。
The combination of photodynamic therapy (PDT) and chemotherapy holds great potential in combating drug-resistant cancers. However, the major challenge that lies ahead is how to achieve high coloading capacity for both photosensitizer and chemo-drugs and how to gain efficient delivery of drugs to the drug-resistant tumors. In this study, we prepared a nanovehicle for codelivery of photosensitizer (pyropheophorbide-a, PPa) and chemo-drugs (paclitaxel, PTX) based on the synthesis of PPa-conjugated amphiphilic copolymer PPa-PLA-PEG-PLA-PPa. The obtained nano particles (PP NP) exhibited a satisfactory high drug-loading capacity for both drugs. To achieve effective tumor-targeting therapy, the surface of PP NP was decorated with a tumor homing and penetrating peptide F3. In vitro cellular experiments showed that F3-functionalized PP NP (F3-PP NP) exhibited higher cellular association than PP NP and resulted in the strongest antiproliferation effect. In addition, compared with the unmodified nanoparticles, F3-PP NP exhibited a more preferential enrichment at the tumor site. Pharmacodynamics evaluation in vivo demonstrated that a longer survival time was achieved by the tumor-bearing mice treated with PP NP (+laser) than those treated with chemotherapy only or PDT only. Such antitumor efficacy of combination therapy was further improved following the F3 peptide functionalization. Collectively, these results suggested that targeted combination therapy may pave a promising way for the therapy of drug-resistant tumor.