Biomimetic Platform Based on Mesoporous Platinum for Multisynergistic Cancer Therapy
Photothermal therapy (PTT) using nanoparticles is one of the research hotspots in the field of cancer therapy. However, the thermal resistance of tumor cells and the elimination of nanoparticles by the body’s immune system reduce their therapeutic effect. Therefore, it is essential to reduce heat resistance, improve their biocompatibility, and reduce the clearance of the immune system. In this work, they constructed a biomimetic platform for cancer therapy based on heat shock protein (HSP) inhibitors, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG))-loaded and platelet membrane (PM)-coated mesoporous platinum nanoparticles (MPNPs). First, MPNPs with the properties of chemotherapy and PTT were synthesized to load 17-DMAG (17-DMAG/MPNPs). Then, they were coated with PM for tumor targeting and improved biocompatibility to obtain the final bionic nanotherapy platform 17-DMAG/MPNPs@PM. The results in vivo and in vitro showed that 17-DMAG/MPNPs@PM could accumulate in the tumor and effectively inhibit the growth of tumor cells. Therefore, the biomimetic nanotherapy system is expected to provide new ideas for cancer treatment.
Schematic Illustration of the Structure and Function of 17-DMAG/MPNPs@PM
Photothermal therapy (PTT) is a method for cancer treatment, which uses materials with high photothermal conversion efficiency to kill cancer cells upon light irradiation. Photothermal materials can convert light energy into heat when they are exposed to an external light source. Therefore, photothermal conversion materials play an important role in PTT. Previous reports show that many nanoparticles with photothermal effects including Au, CuS, carbon, boron, and W18O49 have been widely used for the photothermal treatment of cancer. Although significant progress has been made using the above materials in PTT, there are still some obstacles. For example, carbon nanorods have poor absorption capacity in the near-infrared region and poor dispersion in water; CuS has lower photothermal conversion efficiency and causes more obvious systemic toxicity; and W18O49 easily oxidizes into ions losing its photosensitizer effect and causing negative effects in normal tissues.
(A,B) TEM images of MPNPs and 17-DMAG/MPNPs@PM. Scale bar = 50 nm. (C) BET of MPNPs. (D) Analysis of CD41, CD61, GPIbα, and P-selectin proteins in PM and 17-DMAG/MPNPs@PM by western blotting. (E) Size. (F) Zeta potentials.
Ag and Pt have more excellent photothermal conversion efficiency than Au. Especially, mesoporous platinum nanoparticles (MPNPs) possessed a high photothermal efficiency and photoacoustic imaging function. Moreover, it could be degraded to Pt2+ in intracellular acidic organelles, and Pt2+ could damage DNA to exert chemotherapeutic effects on cancer cells.
(A–D) TEM of MPNPs in acid buffer (pH 5.0) at different times. Scale bar = 100 nm. (E) TEM of MPNPs in PBS (pH 7.4). Scale bar = 100 nm. (F) Size of 17-DMAG/MPNPs@PM in PBS, water, and serum for 1 week
In summary, MPNPs could not only produce PTT and chemotherapeutic effects, but also have the function of photoacoustic imaging to monitor their distribution in the body. However, under high-temperature conditions, heat shock proteins (HSPs) would be overexpressed in cancer cells. HSPs inhibited PTT-induced cell apoptosis and caused cell thermal resistance, which could weaken the PTT effect. To solve this problem, HSP inhibitors have been used to reduce the production of HSPs. 17-dimethy-laminoethylamino-17-demethoxygeldanamycin (17-DMAG) is an effective HSP 90 inhibitor. Compared with other HSP 90 inhibitors, it has better solubility and bioavailability, lower toxicity, and higher safety. Therefore, combining PTT with HSP inhibitors may be a potential strategy to improve the efficiency of PTT.
(A) UV–vis spectra. (B) Temperature change curves of the 17-DMAG/MPNPs@PM solution at different powers. (C) Temperature change curves of the 17-DMAG/MPNPs@PM solution with different concentrations. (D) The release rate of 17-DMAG under NIR irradiation and acidic conditions.
For a nanodrug delivery system, the features of poor tissue compatibility, easy removal, a short circulation time, and the lack of active targeting in the body limited its application in terms of cancer treatment. It was reported that biofilm-encapsulated nanoparticles were commonly used as a bionic nano-delivery system to overcome the above shortcomings, which could avoid the body’s immune clearance and significantly extend their circulation time in the body. The biofilm included the cancer cell membrane, red blood cell membrane, platelet membrane (PM), etc. Particularly, platelet membrane-covered nanosystems have attracted more and more attention due to their ability to simulate platelet aggregation to the bleeding site, immune escape, and tumor cell adhesion.
(A,B) Uptake of 17-DMAG/MPNP@PM by MCF-7 cells. Scale bar = 50 μm. (C) Live/dead assay of MCF-7 cells. Scale bar = 400 μm. (D) Survival rate of MCF-7 cells. (E,F) Western blot analysis of HSP 90 protein expression in different treatment groups in MCF-7 cells and quantitative analysis. (Mean ± SD, n = 3. *P < 0.05, **P < 0.01, ***P < 0.001).
(A,B) Near-infrared thermal images and temperature curves of mice. (C) In vivo IVIS imaging of mice at different times. (D,E) Fluorescence imaging and quantitative average signal of major organs. (Mean ± SD, n = 3. *P < 0.05, **P < 0.01, ***P < 0.001).
(A) Schematic diagram of animal experiment. (B) Tumor-bearing mice of different groups before and after treatment. (C) Tumors removed from mice after treatment. (D) Changes of the tumor volume. (E) Tumor weight after treatment. (F) Changes of the body weight. (G) H&E staining images of tumor. (H) TUNEL images of mouse tumor. (I) Expression of the HSP 90 in tumor tissues. Scale bar = 50 μm. (Mean ± SD, n = 3. *P < 0.05, **P < 0.01, ***P < 0.001).
In this study,they synthesized 17-DMAG/MPNPs@PM for combined PTT/chemotherapy The results showed that MPNPs had a higher photothermal conversion efficiency. The combination of HSP 90 inhibitors reduced the thermal resistance of cells and enhanced the photothermal treatment effect. The covering of PM could enhance the biocompatibility and tumor targeting of nanoparticles. The biomimetic platform based on mesoporous platinum showed good antitumor effect both in vitro and in vivo.
Biomimetic Platform Based on Mesoporous Platinum for Multisynergistic Cancer Therapy Gaoqian Zhao, Jiaxin Li, Fangfang lv, Xiaochun Wang, Qing Dong, Dandan Liu, Jinchao Zhang, Zhenhua Li, Xiaohan Zhou, and Huifang Liu ACS Biomaterials Science & Engineering 2021 7 (11), 5154-5164 DOI: 10.1021/acsbiomaterials.1c00912