Co-delivery of nanoparticle and molecular drug by hollow mesoporous organosilica for tumor-activated and photothermal-augmented chemotherapy of breast cancer

Haixian Zhang,Feifei Song,Cai Chang,Yu Chen,Luodan Yu,Caihong Dong

doi:10.1186/s12951-021-01025-w

Abstract

BackgroundIn comparison with traditional therapeutics, it is highly preferable to develop a combinatorial therapeutic modality for nanomedicine and photothermal hyperthermia to achieve safe, efficient, and localized delivery of chemotherapeutic drugs into tumor tissues and exert tumor-activated nanotherapy. Biocompatible organic–inorganic hybrid hollow mesoporous organosilica nanoparticles (HMONs) have shown high performance in molecular imaging and drug delivery as compared to other inorganic nanosystems. Disulfiram (DSF), an alcohol-abuse drug, can act as a chemotherapeutic agent according to its recently reported effectiveness for cancer chemotherapy, whose activity strongly depends on copper ions.ResultsIn this work, a therapeutic construction with high biosafety and efficiency was proposed and developed for synergistic tumor-activated and photothermal-augmented chemotherapy in breast tumor eradication both in vitro and in vivo. The proposed strategy is based on the employment of HMONs to integrate ultrasmall photothermal CuS particles onto the surface of the organosilica and the molecular drug DSF inside the mesopores and hollow interior. The ultrasmall CuS acted as both photothermal agent under near-infrared (NIR) irradiation for photonic tumor hyperthermia and Cu2+ self-supplier in an acidic tumor microenvironment to activate the nontoxic DSF drug into a highly toxic diethyldithiocarbamate (DTC)-copper complex for enhanced DSF chemotherapy, which effectively achieved a remarkable synergistic in-situ anticancer outcome with minimal side effects.ConclusionThis work provides a representative paradigm on the engineering of combinatorial therapeutic nanomedicine with both exogenous response for photonic tumor ablation and endogenous tumor microenvironment-responsive in-situ toxicity activation of a molecular drug (DSF) for augmented tumor chemotherapy.Graphical abstract

Highlights

In comparison with traditional therapeutics, it is highly preferable to develop a combinatorial therapeutic modality for nanomedicine and photothermal hyperthermia to achieve safe, efficient, and localized delivery of chemotherapeutic drugs into tumor tissues and exert tumor-activated nanotherapy
Sulfhydryl groups were added to the as-synthesized hollow mesoporous organosilica nanoparticles (HMONs) via typical 3-mercaptopropyltrimethoxysilane (MPTMS) grafting (HMONs-SH), thereby obtaining multifunctional theranostic nanosystems
The average size of the HMONs was approximately 73.4 nm as tested by dynamic light scattering (DLS), which increased to 98.4 nm due to CuS conjugation (Fig. 2d)

Summary

Introduction

In comparison with traditional therapeutics, it is highly preferable to develop a combinatorial therapeutic modality for nanomedicine and photothermal hyperthermia to achieve safe, efficient, and localized delivery of chemotherapeutic drugs into tumor tissues and exert tumor-activated nanotherapy. Biocompatible organic–inorganic hybrid hollow mesoporous organosilica nanoparticles (HMONs) have shown high performance in molecular imaging and drug delivery as compared to other inorganic nanosystems. Disulfiram (DSF), an alcohol-abuse drug, can act as a chemotherapeutic agent according to its recently reported effectiveness for cancer chemotherapy, whose activity strongly depends on copper ions. Drug delivery nanosystems have been employed for efficient cancer diagnosis and treatment, since the significant development of nanobiotechnology applications [1–8] These organic and inorganic nanoplatforms are multifunctional, have excellent biocompatibility, have relatively high stability in bodily fluids, and have the capacity for the controlled release of therapeutic agents from the nanocarriers in the desired sites, toward tumor cells [9–18]. Biocompatible organic–inorganic hybrid hollow mesoporous organosilica nanoparticles (HMONs) have shown high performance in molecular imaging and drug delivery as compared with other inorganic nanosystems [19–24]. DSF-based chemotherapy is largely dependent on the number of C u2+ ions present at the tumor site, which can maximize the chemotherapeutic efficacy of DSF [32, 33, 35–39]

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Conclusion