Immunotherapies for locally aggressive cancers.

Improving surgical resection outcomes for locally aggressive tumors is key to inducing durable locoregional disease control and preventing progression to metastatic disease. Macroscopically complete resection of the tumor is the standard of care for many cancers, including breast, ovarian, lung, sarcoma, and mesothelioma. Advancements in cancer diagnostics are increasing the number of surgically eligible cases through early detection.

Decreased Lung Metastasis in Triple Negative Breast Cancer Following Locally Delivered Supratherapeutic Paclitaxel-Loaded Polyglycerol Carbonate Nanoparticle Therapy.

Breast cancer is among the most prevalent malignancies, accounting for 685,000 deaths worldwide in 2020, largely due to its high metastatic potential. Depending on the stage and tumor characteristics, treatment involves surgery, chemotherapy, targeted biologics, and/or radiation therapy. However, current treatments are insufficient for treating or preventing metastatic disease.

Engineered bacteria guide T cells to tumors.

T cells and bacteria are engineered to work together to find and destroy tumor cells.

Boolean logic in synthetic biology and biomaterials: Towards living materials in mammalian cell therapeutics.

Background: The intersection of synthetic biology and biomaterials promises to enhance safety and efficacy in novel therapeutics. Both fields increasingly employ Boolean logic, which allows for specific therapeutic outputs (e.g.

Doxorubicin-Loaded Polymeric Meshes Prevent Local Recurrence after Sarcoma Resection While Avoiding Cardiotoxicity.

Unlabelled: Surgery is the only potentially curative treatment for localized soft-tissue sarcomas. However, for sarcomas arising in the retroperitoneum, locoregional recurrence rates are 35% to 59% despite resection. Doxorubicin (DOX) is the standard first-line systemic chemotherapy for advanced soft-tissue sarcoma, yet its intravenous administration yields limited clinical efficacy and results in dose-limiting cardiotoxicity.

Synthesis of bioactive (1→6)-β-glucose branched poly-amido-saccharides that stimulate and induce M1 polarization in macrophages.

β-Glucans are of significant interest due to their potent antitumor and immunomodulatory activities. Nevertheless, the difficulty in purification, structural heterogenicity, and limited solubility impede the development of structure-property relationships and translation to therapeutic applications. Here, we report the synthesis of a new class of (1→6)-β-glucose-branched poly-amido-saccharides (PASs) as β-glucan mimetics by ring-opening polymerization of a gentiobiose-based disaccharide β-lactam and its copolymerization with a glucose-based β-lactam, followed by post-polymerization deprotection.

Ultra-high drug loading improves nanoparticle efficacy against peritoneal mesothelioma.

Peritoneal mesothelioma is an aggressive disease with a median survival of under three years, due to a lack of effective treatment options. Mesothelioma is traditionally considered a "chemoresistant" tumor; however, low intratumoral drug levels coupled with the inability to administer high systemic doses suggests that therapeutic resistance may be due to poor drug delivery rather than inherent biology. While patient survival may improve with repetitive local intraperitoneal infusions of chemotherapy throughout the perioperative period, these regimens carry associated toxicities and significant peri-operative morbidity.

Biomimetic peptide display from a polymeric nanoparticle surface for targeting and antitumor activity to human triple-negative breast cancer cells.

While poly(lactic-co-glycolic acid)-block-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) can encapsulate drug cargos and prolong circulation times, they show nonspecific accumulation in off-target tissues. Targeted delivery of drugs to tumor tissue and tumor vasculature is a promising approach for treating solid tumors while enhancing specificity and reducing systemic toxicity. AXT050, a collagen-IV derived peptide with both antitumor and antiangiogenic properties, is shown to bind to tumor-associated integrins with high affinity, which leads to targeted accumulation in tumor tissue.