Fabrication, evaluation and applications of dissolving microneedles.

Abstract The escape of bladder cancer from immunosurveillance causes monotherapy to exhibit poor efficacy; therefore, designing a multifunctional nanoparticle that boosts programmed cell death and immunoactivation has potential as a treatment strategy. Herein, we developed a facile one-pot coprecipitation reaction to fabricate cluster-structured nanoparticles (CNPs) assembled from Fe 3 O 4 and iron chlorophyll (Chl/Fe) photosensitizers. This nanoassembled CNP, as a multifunctional theranostic agent, could perform red-NIR fluorescence and change the redox balance by the photoinduction of reactive oxygen species (ROS) and attenuate iron-mediated lipid peroxidation by the induction of a Fenton-like reaction. The intravesical instillation of Fe 3 O 4 @Chl/Fe CNPs modified with 4-carboxyphenylboronic acid (CPBA) may target the BC wall through glycoproteins in the BC cavity, allowing local killing of cancer cells by photodynamic therapy (PDT)-induced singlet oxygen and causing chemodynamic therapy (CDT)-mediated ferroptosis. An interesting possibility is reprogramming of the tumor microenvironment from immunosuppressive to immunostimulatory after PDT-CDT treatment, which was demonstrated by the reduction of PD-L1 (lower “off” signal to the effector immune cells), IDO-1, TGF-β, and M2-like macrophages and the induction of CD8 + T cells on BC sections. Moreover, the intravesical instillation of Fe 3 O 4 @Chl/Fe CNPs may enhance the large-area distribution on the BC wall, improving antitumor efficacy and increasing survival rates from 0 to 91.7%. Our theranostic CNPs not only demonstrated combined PDT-CDT-induced cytotoxicity, ROS production, and ferroptosis to facilitate treatment efficacy but also opened up new horizons for eliminating the immunosuppressive effect by simultaneous PDT-CDT. 

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Iron oxide@chlorophyll clustered nanoparticles eliminate bladder cancer by photodynamic immunotherapy-initiated ferroptosis and immunostimulation

Immune checkpoint blockade (ICB) therapy has evolved as a revolutionized therapeutic modality to eradicate tumor cells by releasing the brake of the antitumor immune response. However, only a subset of patients could benefit from ICB treatment currently. Phototherapy usually includes photothermal therapy (PTT) and photodynamic therapy (PDT). PTT exerts a local therapeutic effect by using photothermal agents to generate heat upon laser irradiation. PDT utilizes irradiated photosensitizers with a laser to produce reactive oxygen species to kill the target cells. Both PTT and PDT can induce immunogenic cell death in tumors to activate antigen-presenting cells and promote T cell infiltration. Therefore, combining ICB treatment with PTT/PDT can enhance the antitumor immune response and prevent tumor metastases and recurrence. In this review, we summarized the mechanism of phototherapy in cancer immunotherapy and discussed the recent advances in the development of phototherapy combined with ICB therapy to treat malignant tumors. Moreover, we also outlined the significant progress of phototherapy combined with targeted therapy or chemotherapy to improve ICB in preclinical and clinical studies. Finally, we analyzed the current challenges of this novel combination treatment regimen. We believe that the next-generation technology breakthrough in cancer treatment may come from this combinational win-win strategy of photoimmunotherapy.

Combination of phototherapy with immune checkpoint blockade: Theory and practice in cancer

Noble metal nanoparticles have been sought after in cancer nanomedicine during the past two decades, owing to the unique localized surface plasmon resonance that induces strong absorption and scattering properties of the nanoparticles. A popular application of noble metal nanoparticles is photothermal therapy, which destroys cancer cells by heat generated by laser irradiation of the nanoparticles. Gold nanorods have stood out as one of the major types of noble metal nanoparticles for photothermal therapy due to the facile tuning of their optical properties in the tissue penetrative near infrared region, strong photothermal conversion efficiency, and long blood circulation half-life after surface modification with stealthy polymers. In this review, we will summarize the optical properties of gold nanorods and their applications in photothermal therapy. We will also discuss the recent strategies to improve gold nanorod-assisted photothermal therapy through combination with chemotherapy and photodynamic therapy.

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Gold Nanorod-Assisted Photothermal Therapy and Improvement Strategies

Breast cancer (BC) has different clinical manifestations due to its diverse mechanism of action that has created many challenges to choosing appropriate treatment. Recent findings of the biology of breast cancer including the mechanisms of survival and metastasis, understanding the effective signaling pathways in tumor formation and modeling of cancer cell responses to the therapeutic approaches provided significant advances in BC treatment. In this regard, the use of phototherapy-based approaches such as photothermal therapy (PTT) would be an encouraging alternative for tumor suppression through activating autophagy or suppressing cell signaling that influences the cell cycle to induce cell death. Since autophagy has a dual opposite role consisting of pro-survival and growth inhibition in breast cancer microenvironments, the regulation of autophagy would be playing promising roles in the treatment of BC using PTT. This review updates the molecular mechanisms that PTT could evoke autophagic cell death in breast cancer. Moreover, this article provides insights into the biological effects of autophagy-targeted-PTT as a promising strategy for breast cancer therapy. 

Photothermal therapy-mediated autophagy in breast cancer treatment: Progress and trends.

Application of molecular docking in elaborating molecular mechanisms and interactions of supramolecular cyclodextrin.

Engineered nanomaterials for synergistic photo-immunotherapy.

Development of gold nanorods for cancer treatment.

As a painless and minimally invasive method of self-administration, microneedle is very promising to replace subcutaneous injection of insulin for type I diabetes treatment. Since the introduction of microneedles, many scholars have paid attention to and studied this technology, which has made it developed rapidly. However, there is no product on the market or in clinical trials at present. The reason is that there are still many technical problems in microneedle drug delivery system, such as the perfect integration of stable, controllable, fast, long-lasting, safe, and other necessary conditions. Here, we review the achievements that researchers have made that contain one or more of the above factors, and put some ideas to solve the limitations of insulin delivery by microneedles for reference.

Design and development of insulin microneedles for diabetes treatment.

Hydrogel is a kind of 3D polymer network with strong swelling ability in water and appropriate mechanical and biological properties, which make it feasible to maintain bioactive substances and has promising applications in the fields of biomaterials, soft machines, and artificial tissues. Unfortunately, traditional hydrogels prepared by chemical crosslinking have poor mechanical properties and limited functions, which limit their further application. In recent years, with the continuous development of nanoparticle research, more and more studies have combined nanoparticles with hydrogels to make up for the shortcomings of traditional hydrogels. In this article, the types and functions of hydrogels and nanomaterials are introduced first, as well as the functions and applications of injectable nanocomposite hydrogels (INHs), then the latest progress of INHs for cancer treatment is reviewed, some existing problems are summarized, and the application prospect of NHs is prospected.

Qida Zong

Papers

Application of molecular docking in elaborating molecular mechanisms and interactions of supramolecular cyclodextrin.

Engineered nanomaterials for synergistic photo-immunotherapy.

Development of gold nanorods for cancer treatment.

Design and development of insulin microneedles for diabetes treatment.

Injectable Nanocomposite Hydrogels for Cancer Therapy.