Nano Today recently published a paper entitled “In Situ Phagocyte-mediated Deep Tumor Penetration Assisted by ApoA-1 Mimetic Peptide-modified Silicasome”. The paper comes from Prof. Zhihong Zhang’s research group.
Malignant tumors have surpassed cardiovascular diseases and become the deadliest, seriously threatening human health and life. Since solid tumors display remarkable heterogeneity, hypoxia, insufficient blood supply and increased interstitial fluid pressure, most nanomedicines cannot sufficiently penetrate into the tumor with a thorough distribution, leading to limited diagnosis and therapeutic efficacy. The development of deep penetration of therapeutic systems remains a challenge for cancer therapy. In general, strategies of deep penetration of nanomedicines can be divided into two categories: one is based on an exquisitely designed nanoplatform, including CAPIR five-step cascade delivery (circulation, accumulation, penetration, internalization and release) and size shrinkage delivery by using extravasation of blood vessels, increased tumor interstitial osmotic pressure, enhanced permeability and retention (EPR) effect to deeply penetrate into the tumor; the other is cell-mediated drug delivery (also known as the Trojan horse strategy) with the application of the physiological functions of living cells and artificial cells loaded with nanoparticles to achieve specific delivery to tumor regions. However, due to the time-consuming process of the design and preparation of nanoplatform systems and the heterogeneity of tumor, their clinical application is hindered. Therefore, it is acquisitive to create straightforward and affordable NPs, integrating advantages of multiple strategies, to promote the penetration of nanodrugs into the tumor that can facilitate clinical translation.
Figure1.Schematic illustrationofR4F-ICG@L-MSNs for deep tumor penetration and efficient photothermal therapy.
Recently, the research team led by Prof. Zhihong Zhang developed an apoA-1 mimetic peptide (R4F) modified silicasome (R4F-ICG@L-MSNs) for deep penetration and wide distribution in tumors. The R4F peptide incorporated into the lipid layers enables both high uptake by phagocytes in peripheral blood and effective residence in tumor and macrophages via the SR-B1 receptor, termed R4F ICG@L-MSN (Figure 1). Owing to intrinsic phagocytotic capability and tumor-homing property of phagocyte, R4F-ICG@L-MSN could be efficiently transported via in situ phagocyte-mediated delivery strategy, with promoted deep infiltration of the tumor for the tumor-homing properties of the phagocyte. The PA imaging confirmed the deep tumor penetration and enhanced cell-uptake, resulting in the efficient residence in tumor of R4F-ICG@L-MSN throughout the tumor area (Figure 2). Consequently, R4F-ICG@L-MSN manifest perfect therapeutic efficacy as verified in the photothermal therapy, accompanied by a reverse immunosuppressive microenvironment, including stimulating the maturation of dendritic cells and promoting the infiltration of CD8+T cells .
Such an intelligent nanoparticle has achieved high performance of deep penetration, tumor targeting, PA imaging-guided PTT andanti-tumorimmune response, providing high translation potential in the clinic. By using in situ phagocyte-mediated transport and tumor-targeting accumulation strategies to deliver theranostic drugs in tumors, this work also presents a viable way to eliminate solid tumors, which may be highly beneficial to future nanomedicine design.
Figure 2. Biomimetic R4F modified silicasome enables tumor deep penetration and exhaustive biodistribution.
Prof. Zhihong Zhang and Prof. Xiaoquan Yang are the co-corresponding authors. Postdoc. Junjie Wang from ZZH research group and Associate Prof. Xingzhou Peng from Hainan University are the co-first authors of the article. This work was supported by the National Science Foundation of China (81625012), the Open Project Program of Wuhan National Laboratory for Optoelectronics (NO.2021WNLOKF008), the Hainan Provincial Natural Science Foundation of China (823RC472), the Hainan University Scientific Research Foundation (KYQD(ZR)20078) and (KYQD(ZR)19107), and the Fundamental Research Funds for the Central Universities (2019kfyXMBZ022).
Link: https://www.sciencedirect.com/science/article/pii/S1748013223001135?dgcid=coauthor
