Recent trends of mesoporous silica-based nanoplatforms for nanodynamic therapies

Conventional cancer chemotherapies often exhibit insufficient therapeutic outcomes and dose-limiting toxicity. Therefore, there is a need for novel therapeutics and formulations with higher efficacy, improved safety, and more favorable toxicological profiles. This has promoted the development of nanomedicines, including systems for drug delivery, but also for imaging and diagnostics. Nanoparticles loaded with drugs can be designed to overcome several biological barriers to improving efficiency and reducing toxicity. In addition, stimuli-responsive nanocarriers are able to release their payload on demand at the tumor tissue site, preventing premature drug loss. This review focuses on ultrasound-triggered drug delivery by nanocarriers as a versatile, cost-efficient, non-invasive technique for improving tissue specificity and tissue penetration, and for achieving high drug concentrations at their intended site of action. It highlights aspects relevant for ultrasound-mediated drug delivery, including ultrasound parameters and resulting biological effects. Then, concepts in ultrasound-mediated drug delivery are introduced and a comprehensive overview of several types of nanoparticles used for this purpose is given. This includes an in-depth compilation of the literature on the various in vivo ultrasound-responsive drug delivery systems. Finally, toxicological and safety considerations regarding ultrasound-mediated drug delivery with nanocarriers are discussed.

https://www.mdpi.com/1999-4923/13/8/1135/pdf

Drug Delivery by Ultrasound-Responsive Nanocarriers for Cancer Treatment

Chlorin e6 (Ce6) has been extensively researched and developed as an antitumor therapy. Ce6 is a highly effective photosensitizer and sonosensitizer with promising future applications in photodynamic therapy, dynamic acoustic therapy, and combined acoustic and light therapy for tumors. Ce6 is also being studied for other applications in fluorescence navigation, antibacterials, and plant growth regulation. Here we review the role and research status of Ce6 in tumor therapy and the problems and challenges of its clinical application. Other biomedical effects of Ce6 are also briefly discussed. Despite the difficulties in clinical application, Ce6 has significant advantages in photodynamic therapy (PDT)/sonodynamic therapy (SDT) against cancer and offers several possibilities in clinical utility.

Antitumor Effect of Photodynamic Therapy/Sonodynamic Therapy/Sono-Photodynamic Therapy of Chlorin e6 and Other Applications.

This review focuses on the biomedical application of mesoporous silica nanoparticles (MSNs), mainly focusing on the therapeutic application of MSNs for cancer treatment and specifically on overcoming the challenges of currently available anthelmintics (e.g., low water solubility) as repurposed drugs for cancer treatment. MSNs, due to their promising features, such as tunable pore size and volume, ability to control the drug release, and ability to convert the crystalline state of drugs to an amorphous state, are appropriate carriers for drug delivery with the improved solubility of hydrophobic drugs. The biomedical applications of MSNs can be further improved by the development of MSN-based multimodal anticancer therapeutics (e.g., photosensitizer-, photothermal-, and chemotherapeutics-modified MSNs) and chemical modifications, such as poly ethyleneglycol (PEG)ylation. In this review, various applications of MSNs (photodynamic and sonodynamic therapies, chemotherapy, radiation therapy, gene therapy, immunotherapy) and, in particular, as the carrier of anthelmintics for cancer therapy have been discussed. Additionally, the issues related to the safety of these nanoparticles have been deeply discussed. According to the findings of this literature review, the applications of MSN nanosystems for cancer therapy are a promising approach to improving the efficacy of the diagnostic and chemotherapeutic agents. Moreover, the MSN systems seem to be an efficient strategy to further help to decrease treatment costs by reducing the drug dose.

/pdf/application-of-mesoporous-silica-nanoparticles-in-cancer-3nu9e8pt.pdf

Application of Mesoporous Silica Nanoparticles in Cancer Therapy and Delivery of Repurposed Anthelmintics for Cancer Therapy

Sonodynamic therapy (SDT) represents a promising therapeutic modality for treating breast cancer, which relies on the generation of abundant reactive oxygen species (ROS) to induce oxidative stress damage. However, mutant breast cancers, especially triple‐negative breast cancer (TNBC), have evolved to acquire specific antioxidant defense functions, significantly limiting the killing efficiency of SDT. Herein, the authors have engineered a distinct single copper atom‐doped titanium dioxide (Cu/TiO2) nanosonosensitizer with highly catalytic and sonosensitive activities for synergistic chemodynamic and sonodynamic treatment of TNBC. The single‐atom Cu is anchored on the most stable Ti vacancies of hollow TiO2 sonosensitizers, which not only substantially improved the catalytic activity of Cu‐mediated Fenton‐like reaction, but also considerably augmented the sonodynamic efficiency of TiO2 by facilitating the separation of electrons (e−) and holes (h+). Both the in vitro and in vivo studies demonstrate that the engineered single atom‐doped nanosonosensitizers effectively achieved the significantly inhibitory effect of TNBC, providing a therapeutic paradigm for non‐invasive and safe tumor elimination through the mutual process of sono/chemo‐nanodynamic therapy based on multifunctional single‐atom nanosonosensitizers.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202206244

Single Atom‐Doped Nanosonosensitizers for Mutually Optimized Sono/Chemo‐Nanodynamic Therapy of Triple Negative Breast Cancer

Introduction Sonodynamic Therapy (SDT) has good targeting and non-invasive advantages in solid cancers, but its antitumor effect is not sufficient to replace traditional treatments. Some studies that combined SDT with chemotherapy or nanoparticles have managed to enhance its efficiency and overcome the side effects of chemotherapy. Materials and methods In this study, we synthesized and characterized mesoporous silica nanoparticles (MSN-DOX-Ce6) loaded with doxorubicin (DOX) and sonosensitizer, chlorin e6 (Ce6). Then, we conducted in vitro and in vivo experiments to explore the antitumor effect of MSN-DOX-Ce6 under ultrasound (US) treatment. Results The characterization tests showed that the nanoparticles are uniformly sized spheres with mesoporous structure, resulting in a high drug-loading efficiency. In the in vitro experiments, MSN-DOX-Ce6 could effectively inhibit cell proliferation under US but not more than other treatment groups. However, the in vivo studies showed that MSN-DOX-Ce6+US has better antitumor effect than DOX+Ce6+US or DOX alone on xenograft tumor-bearing mice. Conclusion In summary, MSNs showed a great potential for DOX and Ce6 delivery. We concluded that under US, MSN-DOX-Ce6 nanocomposites increase the antitumor effect of DOX and SDT and thereby are a potential treatment for solid tumors.

/pdf/therapeutic-effect-of-doxorubicin-chlorin-e6-loaded-48ys8tw70h.pdf

Therapeutic Effect of Doxorubicin-Chlorin E6-Loaded Mesoporous Silica Nanoparticles Combined with Ultrasound on Triple-Negative Breast Cancer.

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Therapeutic Effect of Doxorubicin-Chlorin E6-Loaded Mesoporous Silica Nanoparticles Combined with Ultrasound on Triple-Negative Breast Cancer.