Carrier-free nano-integrated strategy of phototherapy and chemotherapy for synergetic AKT targeted therapy to inhibit cancer metastasis and recurrence.

A key challenge in clinical anticancer treatments is metastasis and recurrence, to address this challenge, it is crucial to develop combination treatment strategies that target different molecular pathways, considering the high complexity of tumors, as well as to create efficient drug delivery systems that enhance therapeutic efficacy and minimize systemic toxicity. Herein, two clinical small molecular drugs indocyanine green (ICG) and paclitaxel (PTX) were self-assembled into relatively stable, carrier-free nanoparticles (IP NPs) through a simple one-step nanoprecipitation method. The spherical IP NPs demonstrate excellent aqueous stability, tumor-targeted accumulation, and potent apoptosis induction.

Engineered Probiotics-Based Biohybrid-Driven Tumor Metabolic Remodeling To Boost Tumor Photoimmunotherapy.

Bioengineered probiotics enable new opportunities to address abnormal cancer metabolism and suppressive immune-environment interactions for improved therapeutic susceptibility. Here, Nissle 1917 (EcN) was constructed to convert ammonia into l-arginine continuously and was further modified with polydopamine (PDA) to form living biotherapeutic argEcN@P for enhanced colorectal cancer eradication. Benefiting from the movement of EcN, argEcN@P could colonize and penetrate deep in tumors through hypoxia targeting and increase the intratumoral l-arginine concentrations.

Poly(ethylenimine)-Cyclodextrin-Based Cationic Polymer Mediated HIF-1α Gene Delivery for Hindlimb Ischemia Treatment.

Hindlimb ischemia is a common disease worldwide featured by the sudden decrease in limb perfusion, which usually causes a potential threat to limb viability and even amputation or death. Revascularization has been defined as the gold-standard therapy for hindlimb ischemia. Considering that vascular injury recovery requires cellular adaptation to the hypoxia, hypoxia-inducible factor 1 α (HIF-1α) is a potential gene for tissue restoration and angiogenesis.

Near-Infrared-II Fluorophore with Inverted Dependence of Fluorescence Quantum Yield on Polarity as Potent Phototheranostics for Fluorescence-Image-Guided Phototherapy of Tumors.

Organic phototheranostics simultaneously having fluorescence in the second near-infrared (NIR-II, 1000-1700 nm) window, and photothermal and photodynamic functions possess great prospects in tumor diagnosis and therapy. However, such phototheranostics generally suffer from low brightness and poor photodynamic performance due to severe solvatochromism. Herein, an organic NIR-II fluorophore AS1, which possesses an inverted dependence of fluorescence quantum yield on polarity, is reported to serve as potent phototheranostics for tumor diagnosis and therapy.

Mitochondria Targeted Nanoparticles Potentiate Tumor Chemo-Phototherapy by Toxic Oxidative Stress Mediated Oxeiptosis.

Insufficient accumulation of drug at the tumor site and the low drug response are the main reason for the unsatisfactory effect of cancer therapy. Delivery drugs exquisitely to subcellular level can be employed to reduce side effects, and expand the therapeutic window. Herein, a triphenylphosphine (TPP) modified lipid nanoparticles is designed which are loaded with the photosensitizer indocyanine green (ICG) and chemotherapeutic paclitaxel (PTX) for mitochondria-targeted chemo-phototherapy.

Engineering of small molecular organic nanoparticles for mitochondria-targeted mild photothermal therapy of malignant breast cancers.

Conventional photothermal therapy (PTT) often causes unwanted hyperthermia damage to the surrounding healthy tissues, and fails in the ablation of infiltrating and malignant tumors, which even leads to tumor recurrence. The main reasons for the suboptimal therapeutic efficacy of PTT include: (i) the heterogenous distribution of PTT agents in cancer cells, (ii) the limited penetration depth of irradiation light, and (iii) importantly, the difficulty in controlling the photothermal process which often leads to overheated hyperthermia and severe side effects, including inflammation, immune escape, metastasis and damage to normal tissues surrounding the tumor. It is envisioned that organelle targeted mild PTT would be a good strategy to overcome these shortcomings and significantly improve the therapeutic efficacy, decrease the therapeutic threshold for both the drug dosage and hyperthermia temperature, and diminish damage to the neighboring healthy tissues.

Mitochondria and Endoplastic Reticulum Targeting Strategy for Enhanced Phototherapy.

To ensure improved efficacy and minimized toxicity of therapeutic molecules, it is generally accepted that specifically delivering them to the subcellular site of their action will be attractive. Phototherapy has received considerable attention because of its noninvasiveness, high temporal-spatial resolution, and minimal drug resistance. As important functional organelles in cells, mitochondria and endoplasmic reticulum (ER) participate in fundamental cellular processes, which make them much more sensitive to reactive oxygen species (ROS) and hyperthermia.