Multifunctional Nanosystem for Dual Anti-Inflammatory and Antibacterial Photodynamic Therapy in Infectious Diabetic Wounds.

Infectious diabetic wounds present a substantial challenge, characterized by inflammation, infection, and delayed wound healing, leading to elevated morbidity and mortality rates. In this work, we developed a multifunctional lipid nanoemulsion containing quercetin, chlorine e6, and rosemary oil (QCRLNEs) for dual anti-inflammatory and antibacterial photodynamic therapy (APDT) for treating infectious diabetic wounds. The QCRLNEs exhibited spherical morphology with a size of 51 nm with enhanced encapsulation efficiency, skin permeation, and localized delivery at the infected wound site. QCRLNEs with NIR irradiation have shown excellent wound closure and antimicrobial properties in vitro, mitigating the nonselective cytotoxic behavior of PDT. Also, excellent biocompatibility and anti-inflammatory and wound healing responses were observed in zebrafish models. The infected wound healing properties in S. aureus-infected diabetic rat models indicated re-epithelization and collagen deposition with no signs of inflammation. This multifaceted approach using QCRLNEs with NIR irradiation holds great promise for effectively combating oxidative stress and bacterial infections commonly associated with infected diabetic wounds, facilitating enhanced wound healing and improved clinical outcomes.

Self-assembled IR dye/mitoxantrone loaded Porphysomes nanosystem for enhanced combinatorial chemo-photothermal cancer therapy.

Chemo-photothermal therapy (PTT) is an emerging non-invasive cancer treatment modality. Light-responsive porphysomes (DPP IR Mtx @Lipo NPs) nanosystems ablate breast cancer cells upon oxidative stress and hyperthermia. The unique self-assembled porphysomes were formed spherical shape in the size range of 150 ± 30 nm formed by the co-assembly of porphyrins along with IR 775 and chemotherapeutic drug, Mitoxantrone (Mtx), forming a camouflaged nanosystem (DPP IR Mtx @Lipo NPs, porphysomes). The advent of the prepared porphysomes aids in proper tuning of NIR absorbance improving singlet oxygen species generation among other anticancer drugs. The eminent release of DPP and adjuvant chemo-drug, Mitoxantrone from the self-assembled porphysomes is triggered by IR 775, a NIR photosensitizer upon laser irradiation. These multifunctional DPP IR Mtx @Lipo NPs have an efficient photothermal conversion efficiency of 65.8% as well as bioimaging properties. In-vitro studies in 2D and 3D models showed a significant cell death of 4T1 cells via the apoptotic pathway when irradiated with NIR laser, causing minimal damage to nearby healthy cells. DPP IR Mtx @Lipo NPs exhibited commingled PDT/PTT interdependent via NIR laser exposure, leading to mitochondrial disruption. Interestingly, the transient transfection using p53-GFP in cancer cells followed by DPP IR Mtx @Lipo NPs treatment causes rapid cell death. The activation of p53-dependent apoptosis pathways was vividly expressed, evidenced by the upregulation of Bax and increased pattern of Caspase-3 cleavage. This effect was pronounced upon transfection and induction with DPP IR Mtx @Lipo NPs, particularly in comparison to non-transfected malignant breast cancer 4T1 cells.

Radiotherapy, photodynamic therapy, and cryoablation-induced abscopal effect: Challenges and future prospects.

Local therapy modalities such as radiation therapy, photodynamic therapy, photothermal therapy, and cryoablation have been used to treat localized tumors for decades. The discovery of the abscopal effect causes a paradigm shift where local therapy also causes systemic effects and leads to the remission of nonirradiated tumors. The abscopal effect of radiation therapy, alone or in combination with other treatments, has been extensively studied over the last six decades. However, the results are unsatisfactory in producing robust, reproducible, and long-lasting systemic effects. Although immunotherapy and radiation therapy are promising in producing the abscopal effect, the abscopal effect's mechanism is still unclear, owing to various factors such as irradiation type and dose and cancer type. This article reviews the research progress, clinical and preclinical evidence of the abscopal effect by various local therapies alone and in combination with chemotherapy and immunotherapy, case reports, and the current challenges in producing the abscopal effect by various local therapies, focusing on radiotherapy, photodynamic therapy, cryoablation, and the prospects for obtaining a robust, reproducible, and long-lasting abscopal effect.

IR-775 - Hyptis loaded bioactive nanoparticles for enhanced phyto-photothermal therapy of breast cancer cells.

Photo-responsive therapy is an emerging treatment modality due to its bioimaging and therapeutic properties. Phototherapy induces localized hyperthermia and selectively eradicates cancer cells. The current study showed that multifunctional biodegradable liposome nanosystem (HIL NPs) containing Hyptis suaveolens bioactive molecules and IR-775, a NIR dye showed efficient bioavailability to cancer ells and allowed tumor ablation upon NIR laser irradiation. The resulting entities present in the nanosystem, i.e., bioactive molecules of Hyptis, serve as an anticancer agent, and IR-775 helps in the photothermal ablation of highly metastatic breast cancer cells. Hyptis suaveolens is a weed that grows rampantly, impeding the growth of neighboring plants; nonetheless, its bioactive compounds have demonstrated therapeutic benefits. The obtained HIL NPs, photothermally active liposome nanosystem showed a high fluorescence absorption peak in the NIR range and delivered a photothermal conversion efficiency of 55.20 % upon NIR laser irradiation. TEM and particle size analyzer revealed that HIL NPs have a size of 141 ± 30 nm with a spherical shape. The results of in-ovo (zebrafish) experiments have shown efficient bioimaging capabilities with minimal concentrations of HIL NPs compared to respective controls. Furthermore, in-vitro studies of HIL NPs against triple-negative breast cancer (4T1) indicated effective anticancer activity by a combined cytotoxic effect and hyperthermia. Tumor ablation was facilitated by reactive oxygen species production and hyperthermia, leading to DNA damage and apoptosis due to overexpression of É£-H2AX, Cathepsin B, and p53, which halted cancer cell proliferation. Therefore, HIL NPs demonstrated effective anticancer effects induced by combined phyto-photothermal therapy when evaluated against an in-vitro breast cancer model.

Chlorin e6: A Promising Photosensitizer in Photo-Based Cancer Nanomedicine.

Conventional cancer treatment modalities are often associated with major therapeutic limitations and severe side effects. Photodynamic therapy is a localized noninvasive mode of treatment that has given a different direction to cancer research due to its effectivity against a wide range of cancers and minimal side effects. A photosensitizer is the key component of photodynamic therapy (PDT) that generates cytotoxic reactive oxygen species to eradicate cancer cells. As the therapeutic effectivity of PDT greatly depends upon the photosensitizer, great efforts have been made to search for an ideal photosensitizer. Chlorin e6 is a FDA approved second generation photosensitizer that meets the desired clinical properties for PDT. It is known for its high reactive oxygen species (ROS) generation ability and anticancer potency against many types of cancer. Hydrophobicity is a major drawback of Ce6 that leads to its poor biodistribution and rapid clearance from the circulatory system. To overcome this drawback, researchers have designed and fabricated several types of nanosystems, which can enhance Ce6 solubility and thereby enhance its bioavailability. These nanosystems also improve tumor accumulation of Ce6 by selectively targeting the cancer cells through passive and active targeting. In addition, Ce6 has been employed in many combination therapies like chemo-photodynamic therapy, photoimmunotherapy, and combined photodynamic-photothermal therapy. A combination therapy is more curative than a single therapy due to the synergistic effects of individual therapies. Ce6-based nanosystems for combination therapies have shown excellent results in various studies and provide a promising platform for cancer treatment.

Recent Advancements in the Design of Nanodelivery Systems of siRNA for Cancer Therapy.

RNA interference (RNAi) has increased the possibility of restoring RNA drug targets for cancer treatment. Small interfering RNA (siRNA) is a promising therapeutic RNAi tool that targets the defective gene by inhibiting its mRNA expression and stopping its translation. However, siRNAs have flaws like poor intracellular trafficking, RNase degradation, rapid kidney filtration, off-targeting, and toxicity, which limit their therapeutic efficiency. Nanocarriers (NCs) have been designed to overcome such flaws and increase antitumor activity. Combining siRNA and anticancer drugs can give synergistic effects in cancer cells, making them a significant gene-modification tool in cancer therapy. Our discussion of NCs-mediated siRNA delivery in this review includes their mechanism, limitations, and advantages in comparison with naked siRNA delivery. We will also discuss organic NCs (polymers and lipids) and inorganic NCs (quantum dots, carbon nanotubes, and gold) that have been reported for extensive delivery of therapeutic siRNA to tumor sites. Finally, we will conclude by discussing the studies based on organic and inorganic NCs-mediated siRNA drug delivery systems conducted in the years 2020 and 2021.