巨噬细胞微粒运载纳米光热转换材料靶向肿瘤的近红外光热治疗研究

Nanomaterials mediated photothermal therapy (PTT) is of intriguing interest in the field of cancer therapy. However, the uneven intratumoral distribution and low tumor targeting of the photothermal conversion nanomaterials during photothermal therapy are problems to be solved urgently. As the novel nano-sized endogenous carrier, macrophage derived microvesicles (MMVs) show great tumor targeting behavior as inheriting the recognizing information from their parental cells - macrophages. Moreover, MMVs have the advantages of better biosafety and easy surface modification for enhanced targeting and in vivo tracing. Depending on the experience of the applicant in the field of gold nanorods (AuNRs) mediated photothermal therapy, our project plans to launch the research on the near-infrared photothermal therapy mediated by MMVs delivering photothermal conversion nanomaterials. We will focus on the strategies of loading nanometaterials into the MMVs to maximize the loading efficiency while minimize the damages on the MMVs’ targeting information. Furthermore, by utilizing the phospholipids replacement strategy, we will modify the MMVs with personalized targeting information in order to improve their tumor targeting prosperity and enhance their tumor accumulation, thus to realize better photothermal therapeutic efficacy. The successful accomplishment of our project will allow the photothermal conversion nanomaterials to target the tumor with more efficiency and low toxicity, therefore promoting the translation of photothermal therapy in clinical application.

纳米材料介导的近红外光热治疗是目前肿瘤治疗领域的研究热点之一。纳米光热转换材料本身较低的肿瘤靶向性和非均匀的瘤内分布，是当前光热治疗领域亟待解决的难点问题。巨噬细胞微粒作为一种新型纳米/药物内源性载体，其可继承母细胞表面的生物识别信息，表现出很好的肿瘤靶向聚集行为，且具有生物安全性高、易进行示踪及靶向性改造等优点。本项目依托申请人在金纳米棒光热治疗领域的多年积累，开展巨噬细胞微粒运载金纳米棒靶向肿瘤的近红外光热治疗研究。项目主要研究巨噬细胞微粒装载金纳米棒的方法，在不破坏巨噬细胞微粒原有靶向性的基础上，提高装载效率；并利用“磷脂替换”策略对微粒进行靶向性改造，进一步提高其对肿瘤组织的靶向及渗透能力，以较低的毒副作用实现高效的肿瘤光热治疗。本项目的成功实施，将有助于实现纳米光热转换材料对肿瘤组织高效、低毒的靶向运输，推动肿瘤光热治疗技术的临床应用。

光热治疗具有快速、高效、精准、微创、可控且毒副作用小等优点，是癌症治疗领域的研究热点之一。光热治疗可局部杀伤肿瘤，显著降低了全身毒性反应，是有潜力替代手术的肿瘤治疗技术之一。然而，作为光热治疗载体的纳米颗粒通常对于肿瘤组织缺乏靶向性，其在肿瘤部位的聚集主要依赖于增强渗透滞留效应（EPR)。这种被动滞留效应无法实现纳米材料在肿瘤部位的高效聚集，且难以抵达肿瘤中心，导致光热治疗效果不佳。本研究采用巨噬细胞微粒为金纳米棒载体，探究了多种金纳米棒装载策略，明确可通过“磷脂替换”构建多功能双靶向的微粒载体，通过“top-down”实现金纳米棒的装载，从而构建巨噬细胞微粒运载的金纳米棒用于肿瘤光热治疗。该载体具有较高的肿瘤靶向性，在近红外激光照射下可有效杀伤肿瘤。本项目的研究证实了细胞微粒-这一天然纳米载体的独特优越性，并进行可控改造的优良性状，具有开发潜力。