Polysilsesquioxane nanoparticles for triggered release of cisplatin and effective cancer chemoradiotherapy

Abstract

Chemoradiotherapy is a well-established treatment paradigm in oncology. There has been strong interest in identifying strategies to further improve its therapeutic index. An innovative strategy is to utilize nanoparticle (NP)chemotherapeutics in chemoradiation. Since the most commonly utilized chemotherapeutic with radiotherapy is cisplatin, the development of a NP cisplatin for chemoradiotherapy has the highest potential impact on this treatment. Here, we report the development of a NP comprised of polysilsesquioxane (PSQ) polymer crosslinked by a cisplatin prodrug (Cisplatin-PSQ) and its utilization in chemoradiotherapy using non-small cell lung cancer as a disease model. Cisplatin-PSQ NP has an exceptionally high loading of cisplatin. Cisplatin-PSQ NPs were evaluated in chemoradiotherapy in vitro and in vivo. They demonstrated significantly higher therapeutic efficacy when compared to cisplatin. These results suggest that the Cisplatin-PSQ NP holds potential for clinical translation in chemoradiotherapy.

An Interdisciplinary Computational/Experimental Approach to Evaluate Drug-Loaded Gold Nanoparticle Tumor Cytotoxicity

“…Cisplatin and paclitaxel are two commonly utilized chemotherapeutics for the treatment of non-small-cell lung cancer (NSCLC) [30], inducing DNA adducts and stabilizing microtubules, respectively, thus impairing cell proliferation and inducing apoptosis [31,32]. Studies in vitro have shown the efficacy of cisplatin-and paclitaxel-loaded nanoparticles for treatment of lung cancer [33][34][35].…”

Hybrid Nanoparticles for Cancer Imaging and Therapy

“…These PSQ nanoparticles exhibited superior cytotoxicity to oxaliplatin free drug against four cancer cell lines in vitro and showed anticancer efficacy in human pancreatic xenograft murine models after intravenous injection. Most recently, Lin and coworkers reported a PSQ nanoparticle carrying a cisplatin prodrug and its utilization in chemoradiotherapy using human lung cancer as a disease model [83]. This PSQ nanoparticle has an exceptionally high loading of cisplatin and demonstrated significantly enhanced anticancer efficacy against free cisplatin both in vitro and in vivo with chemoradiotherapy (Fig.…”

Thermosensitive Hydrogel Co-loaded with Gold Nanoparticles and Doxorubicin for Effective Chemoradiotherapy

“…As definitive or adjuvant treatment for cancer, chemoradiotherapy has been shown more effective than sole treatment alone, and new strategies for chemoradiotherapy to enhance the cancer therapeutic effect have been reported over the past few years (2,3). Recent advances in radiosensitizers have offered new opportunities for improving the effectiveness of chemoradiotherapy, in that the presence of radiosensitizers in the tumor would enhance the radiation effect (4).…”

“…Numerous radiosensitizers have long been investigated (3,(5)(6)(7), among which a significant effort is geared towards gold nanoparticles (AuNPs). As a high Z number (Z=79) element, AuNPs have been known to highly absorb X-rays and concentrate radiation absorption.…”