Cai Xiaoqin,Wu Nian,Song Fangxiang,Luo Honghuan,Li Tingxian,Yan Yibing,Li Songye,Li Yan
Combination therapy for cancers can fully utilize each treatment method’s benefits in order to maximize anti-tumor actions and hence produce superior therapeutic outcomes. In this study, HMTNs@PMO@HA composite nanoparticles, a pH/NIR dual-responsive chemo-photothermal platform, were constructed. The hollow mesoporous titanium dioxide nanoparticles (HMTNs) were prepared by silica-protected calcination and alkali etching, and the periodic mesoporous organosilica (PMO) was coated on top of them to improve the biocompatibility, and then modified by hyaluronic acid (HA) to improve the targeting and cellular uptake of the nanoparticles. This chemo-photothermal platform combined the chemotherapeutic drug doxorubicin (DOX) with the photothermal agent indocyanine green (ICG) to investigate their inhibitory effects on breast cancer cells (MCF-7). Drug loading and release experiments revealed that the platform had a high loading rate of doxorubicin and indocyanine green (DOX: 40.21%; ICG: 25.78%), and the cumulative release rate of the drugs increased in an acidic environment. The results of the photothermal effect evaluation in vitro indicated that the nano-platform had a good photothermal effect. Cytotoxicity and apoptosis assays showed that the nanoparticles combined with NIR had a good inhibitory effect on breast cancer cells (cell viability: 27.68%; apoptosis rate: 43.4%). The above results indicated that the combination therapy used by this nano platform provided high therapeutic efficiency for treating tumors and offered a feasible strategy for combining tumor-targeting with chemo-photothermal therapy.
Metal–organic frameworks (MOFs) are unique coordination polymers that have emerged as important candidates for drug delivery in recent years. Herein, we designed a drug delivery system for multi-modal combination therapy (IR-820/DOX@MIL-101-PDA-PEG-F3, simplified as ID@MIL-PPF3). In this study, pH-sensitive nanocarriers MIL-101(Fe) were prepared and loaded with the effective chemotherapy agent doxorubicin (DOX) and the phototherapeutic reagent new indocyanine green (IR-820) using a physical adsorption method. Dopamine was spontaneously polymerized in alkaline solutions to form a hybrid coating on MIL-101(Fe) (denoted as ID@MIL-101-PDA). The surface of ID@MIL-101-PDA was functionalized by the synthesized polymer NH2-PEG-OCH3/F3 to obtain ID@MIL-PPF3. Characterization results show that ID@MIL-PPF3 has a good drug loading rate (27.7%) and photothermal conversion efficiency (28.89%). In addition, Fe3+ released from MIL-101(Fe) can engage in a Fenton-like reaction to generate hydroxyl radicals (˙OH) to realize chemodynamic therapy (CDT). ID@MIL-PPF3 not only demonstrates the ability to intelligently release drugs, but also realizes chemotherapy combined with PDT/PTT/CDT therapy for tumor cells, which was proved by in vitro evaluation. In conclusion, ID@MIL-PPF3 provides a new idea and method for building a multi-modal combination therapy targeted drug delivery platform.
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