Advances in engineering local drug delivery systems for cancer immunotherapy.
Advances in engineering local drug delivery systems for cancer immunotherapy.
复制标题
肿瘤免疫治疗局部给药系统工程研究进展。
DOI：
10.1002/wnan.1632
复制
发表时间：
2020-09
期刊：
影响因子：
--
通讯作者：
Gu Z
中科院分区：
文献类型：
--
作者：
Abdou P;Wang Z;Chen Q;Chan A;Zhou DR;Gunadhi V;Gu Z
Cancer immunotherapy aims to leverage the immune system to suppress the growth of tumors and to inhibit metastasis. The recent promising clinical outcomes associated with cancer immunotherapy have prompted research and development efforts towards enhancing the efficacy of immune checkpoint blockade, cancer vaccines, cytokine therapy, and adoptive T cell therapy. Advancements in biomaterials, nanomedicine, and micro-/nano-technology have facilitated the development of enhanced local delivery systems for cancer immunotherapy, which can enhance treatment efficacy while minimizing toxicity. Furthermore, locally administered cancer therapies that combine immunotherapy with chemotherapy, radiotherapy, or phototherapy have the potential to achieve synergistic antitumor effects. Herein, the latest studies on local delivery systems for cancer immunotherapy are surveyed, with an emphasis on the therapeutic benefits associated with the design of biomaterials and nanomedicines. Recent advances in the fields of molecular pharmaceuticals, biomaterials, and micro-/nano-technology have inspired enhanced local delivery systems for cancer immunotherapy, which can enhance efficacy and minimize the risk of adverse effects caused by systemic toxicity. Local administration using intratumoral injection, peritumoral injection, sprayable gel, or transdermal microneedle array can be effective to overcome potential systemic transport limitations and to enhance the retention time of therapeutics at the diseased site. Local administration also partially addresses the toxicity issue, as locally administered immunotherapeutics often have lower minimum effective doses than those of systemically administered immunotherapeutics. Sustained release formulations, which utilize materials such as hydrogels and micro-/nano-particles, can further address toxicity issues by establishing control over the release kinetics of the encapsulated therapeutic agents and can sometimes directly serve as adjuvants that help increase activation of the immune system. Importantly, compared to the local administration of small molecule chemotherapeutic drugs, local treatment with immunotherapeutics could also have efficacy toward metastasized sites. Locating and injecting internal tumors could be technically challenging, but these challenges could be addressed by imaging-guided injection and minimally invasive surgical techniques. Examples presented in this review show that locally administered immunotherapeutics can induce systemic antitumor responses specific to the tumor antigens at the injection site, and thus can be effective in inhibiting tumor recurrence and metastasis potential. However, detailed in vivo studies of pharmacokinetics and pharmacodynamics should be evaluated, associated with the distant diseased sites. A detailed understanding of the intercellular interactions and signaling molecules in the tumor microenvironment can be leveraged to design combination therapies for synergistic antitumor effects. Therefore, continued research aimed at elucidating the immunological mechanisms that play a role in the establishment and development of tumors is crucial for further progress in the field of cancer immunotherapy. Moreover, for accelerating clinical translation of anticancer immunotherapeutic delivery systems, the rational design of formulations and devices in the initial development phase is crucial, especially regarding issues of biocompatibility of materials, feasibility of large-scale manufacturing, and quality control. The selection of formulations and delivery routes should be tightly linked to the clinical needs. For example, hydrogel- based systems are well-suited to deliver multiple types of therapeutics, such as immune checkpoint antibodies and chemo- therapy small molecules. By altering the chemical composition, properties such as the drug release rate, biocompatibility, degradation triggers, and physical properties of the hydrogel can be tuned to the desired specifications. Nano-/micro- formulations can also be incorporated to adjust these properties. Moreover, the location of the tumor and the disease degree should be carefully considered when selecting the delivery systems. For example, in the case of unresectable melanoma, a transdermal patch might be highly suitable. If only a partial surgical resection is possible, an injectable hydrogel may be suitable to replace the volume removed. If a tumor can be fully resected, a sprayable gel may be preferred to treat the post-surgical site with sufficient area covered. By fine-tuning the selection of therapeutics, formulation, delivery methods, and potential combination with other treatment modalities such as radiotherapy, clinical efficacy and safety can be enhanced. As personalized medicine is emerging as an overarching theme in healthcare, the choice of the most suitable therapeutic agent(s), formulation(s), and delivery method(s) should be tailored for each individual patient. Caption: Recent advances in local delivery systems for cancer immunotherapy show promise for enhancing therapeutic efficacy while minimizing toxicity.
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