One-Step Fabrication of Multifunctional PLGA-HMME-DTX@MnO2 Nanoparticles for Enhanced Chemo-Sonodynamic Antitumor Treatment

Abstract

Background Sonodynamic therapy (SDT) and its synergistic cancer therapy derivatives, such as combined chemotherapy-SDT (chemo-SDT), are promising approaches for tumor treatment. However, the main drawbacks restricting their applications are hypoxia in tumors and the reducing microenvironment or high glutathione (GSH) levels. Methods In this study, a hybrid metal MnO 2 was deposited onto nanoparticles fabricated using poly(lactic-co-glycolic acid) (PLGA), carrying docetaxel (DTX) and the sonosensitizer hematoporphyrin monomethyl ether (HMME) (PHD@MnO 2 ) via a one-step flash nanoprecipitation (FNP) method. Characterization and in vitro and in vivo experiments were conducted to explore the chemo-SDT effect of PHD@MnO 2 and evaluate the synergetic antitumor treatment of this nanosystem. Results When low-power ultrasound is applied, the acquired PHD@MnO 2 , whether in solution or in MCF-7 cells, generated ROS more efficiently than other groups without MnO 2 or those treated via monotherapy. Specifically, GSH-depletion was observed when MnO 2 was introduced into the system. PHD@MnO 2 presented good biocompatibility and biosafety in vitro and in vivo. These results indicated that the PHD@MnO 2 nanoparticles overcame hypoxia in tumor tissue and suppressed the expression of hypoxia-inducible factor 1 alpha (HIF-1α), achieving enhanced chemo-SDT. Conclusion This study provides a paradigm that rationally engineered multifunctional metal-hybrid nanoparticles can serve as an effective platform for augmenting the antitumor therapeutic efficiency of chemo-SDT.

Application of Nanomaterial-Based Sonodynamic Therapy in Tumor Therapy

“…It is worth noting that tumor hypoxia, reductive microenvironments, and high levels of GSH pose significant challenges when combining SDT and chemotherapy. Cao et al developed a multifunctional metal-hybridized nanosystem aimed at enhancing the efficiency of antitumor therapy by combining chemotherapy and SDT (Figure 6A) [108]. They first prepared a nanoparticle (PHD) carrying docetaxel (DTX) and the acoustic sensitizer HMME using polylactic-co-glycolic acid (PLGA).…”

Sonodynamic therapy-based nanoplatforms for combating bacterial infections

“…Sonosensitizer is a fundamental prerequisite in antibacterial SDT, resulting in a chain of reactions under US activation to stimulate bacterial death [32] . Small molecules of organic photosensitizers, such as porphyrin derivatives [33] , chlorin e 6 (Ce6) [34] , indocyanine green (ICG) [35] , [36] , and curcumin [37] , have exhibited potent ROS generation activity with US treatment. Due to the poor solubility, potential phototoxicity, and short blood circulation time of most organic small-molecule reported sonosensitizers, the SDT therapeutic effects of those sonosensitizers were limited applicability in clinics.…”

Tumor microenvironment-regulated drug delivery system combined with sonodynamic therapy for the synergistic treatment of breast cancer

“…[15][16][17] The antitumor effectiveness of oxygen-dependent SDT is signicantly hindered by the prevailing hypoxia in tumors. 18,19 Additionally, oxygen consumption during SDT further aggravates tumor growth and metastasis. [20][21][22] Therefore, the synthesis and development of nanodrug delivery systems (NDDS) with the abilities to modulate TME have become research hotspots in SDT.…”

“…HM can efficiently load both chemotherapeutic drugs and sonosensitizers. 18,24,25 Bovine serum albumin (BSA), a hydrophilic protein, is used to modify the surface of HM via hydrogen bonding to maintain the stability of HM during its circulation in the body, reduce its aggregation, and improve its water solubility and stability. Furthermore, BSA-mediated drug transport via albumin receptors (gp60) can increase drug accumulation in tumors.…”