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新型核-夹层-壳载多柔比星/锌卟啉共载介孔硅纳米粒@ pH 敏感型磷酸钙@聚乙二醇化脂质体用于增强协同化疗-光动力治疗。

Novel Core-Interlayer-Shell DOX/ZnPc Co-loaded MSNs@ pH-Sensitive CaP@PEGylated Liposome for Enhanced Synergetic Chemo-Photodynamic Therapy.

机构信息

Fujian Provincial Key Laboratory of Innovative Drug Target Research School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361002, China.

Key Laboratory of Biomedical Engineering of Fujian Province University/Research Center of Biomedical Engineering of Xiamen Department of Biomaterials, College of Materials, Xiamen University, Xiamen, 361002, China.

出版信息

Pharm Res. 2018 Feb 8;35(3):57. doi: 10.1007/s11095-017-2295-z.

Abstract

PURPOSE

This work was intended to develop novel doxorubicin (DOX)/zinc (II) phthalocyanine (ZnPc) co-loaded mesoporous silica (MSNs)@ calcium phosphate (CaP)@PEGylated liposome nanoparticles (NPs) that could efficiently achieve collaborative anticancer therapy by the combination of photodynamic therapy (PDT) and chemotherapy. The interlayer of CaP could be utilized to achieve pH-triggered controllable drug release, promote the cellular uptake, and induce cell apoptosis to further enhance the anticancer effects.

METHODS

MSNs were first synthesized as core particles in which the pores were diffusion-filled with DOX, then the cores were coated by CaP followed by the liposome encapsulation with ZnPc to form the final DOX/ZnPc co-loaded MSNs@CaP@PEGylated liposome.

RESULTS

A core-interlayer-shell MSNs@CaP@PEGylated liposomes was developed as a multifunctional theranostic nanoplatform. In vitro experiment indicated that CaP could not only achieve pH-triggered controllable drug release, promote the cellular uptake of the NPs, but also generate high osmotic pressure in the endo/lysosomes to induce cell apoptosis. Besides, the chemotherapy using DOX and PDT effect was achieved by the photosensitizer ZnPc. Furthermore, the MSNs@CaP@PEGylated liposomes showed outstanding tumor-targeting ability by enhanced permeability and retention (EPR) effect.

CONCLUSIONS

The novel prepared MSNs@CaP@PEGylated liposomes could serve as a promising multifunctional theranostic nanoplatform in anticancer treatment by synergic chemo-PDT and superior tumor-targeting ability.

摘要

目的

本研究旨在开发新型阿霉素(DOX)/锌(II)酞菁(ZnPc)共载介孔硅(MSNs)@磷酸钙(CaP)@聚乙二醇化脂质体纳米粒(NPs),通过光动力疗法(PDT)和化学疗法的联合作用,高效实现协同抗癌治疗。CaP 的夹层可用于实现 pH 触发的可控药物释放,促进细胞摄取,并诱导细胞凋亡,以进一步增强抗癌效果。

方法

首先合成 MSNs 作为核颗粒,其中孔道扩散填充 DOX,然后用 CaP 包覆核,再用 ZnPc 包封脂质体,形成最终的 DOX/ZnPc 共载 MSNs@CaP@聚乙二醇化脂质体。

结果

开发了一种核-夹层-壳 MSNs@CaP@聚乙二醇化脂质体多功能治疗性纳米平台。体外实验表明,CaP 不仅可以实现 pH 触发的可控药物释放,促进 NPs 的细胞摄取,还可以在内体/溶酶体中产生高渗透压诱导细胞凋亡。此外,通过光敏剂 ZnPc 实现 DOX 的化疗和 PDT 作用。此外,MSNs@CaP@聚乙二醇化脂质体通过增强的通透性和保留(EPR)效应表现出出色的肿瘤靶向能力。

结论

新型 MSNs@CaP@聚乙二醇化脂质体可作为一种有前途的多功能治疗性纳米平台,通过协同化疗-PDT 和优异的肿瘤靶向能力用于癌症治疗。

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