Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, North Carolina 27599, United States.
ACS Appl Bio Mater. 2023 Mar 20;6(3):934-950. doi: 10.1021/acsabm.2c00973. Epub 2023 Feb 15.
With over 2 million cancer cases and over 600,000 cancer-associated deaths predicted in the U.S. for 2022, this life-debilitating disease continuously impacts the lives of people across the nation every day. Therapeutic treatment options for cancer have historically involved chemotherapies to eradicate tumors with cytotoxic mechanisms which can negatively affect the efficacy versus toxicity ratio of treatment. With a need for more directed and therapeutically active options, targeted small-molecule inhibitors and immunotherapies have since emerged to mitigate treatment-associated toxicities. However, aggressive tumors can employ a wide range of defense mechanisms to evade monotherapy treatment altogether, resulting in the recurrence of therapeutically resistant tumors. Therefore, many clinical routines have included combination therapy in which anticancer agents are combined to provide a synergistic attack on tumors. Even with this approach, maximizing the efficacy of cancer treatment is contingent upon the dose of drug that reaches the site of the tumor, so often therapy is administered at the site of a tumor via localized delivery platforms. Commonly used platforms for localized drug delivery include polymeric wafers, nanofibrous scaffolds, and hydrogels where drug combinations can be loaded and delivered synchronously. Attaining synergistic activity from these localized systems is dependent on proper material selection and fabrication methods. Herein, we describe these important considerations for enhancing the efficacy of cancer combination therapy through biodegradable, localized delivery systems.
预计 2022 年美国将有超过 200 万例癌症病例和超过 60 万例与癌症相关的死亡病例，这种使生命衰弱的疾病每天都在持续影响着全国人民的生活。癌症的治疗选择在历史上一直涉及使用细胞毒性机制的化疗来根除肿瘤，这可能会对治疗的疗效与毒性比产生负面影响。由于需要更有针对性和更具治疗活性的选择，因此靶向小分子抑制剂和免疫疗法已经出现，以减轻治疗相关的毒性。然而，侵袭性肿瘤可以采用多种防御机制来完全逃避单一疗法治疗，导致治疗耐药肿瘤的复发。因此，许多临床常规包括联合治疗，其中抗癌药物联合使用，对肿瘤进行协同攻击。即使采用这种方法，最大限度地提高癌症治疗的疗效也取决于到达肿瘤部位的药物剂量，因此通常通过局部递药平台在肿瘤部位进行治疗。局部药物递送常用的平台包括聚合物薄片、纳米纤维支架和水凝胶，其中可以加载和同步递送药物组合。要从这些局部系统中获得协同活性，取决于适当的材料选择和制造方法。本文中，我们将描述通过可生物降解的局部递药系统来增强癌症联合治疗疗效的这些重要考虑因素。
