Biomimetic Aggregation‐Induced Emission Nanodots with Hitchhiking Function for T Cell‐Mediated Cancer Targeting and NIR‐II Fluorescence‐Guided Mild‐Temperature Photothermal Therapy

Abstract

Photothermal therapy (PTT) holds potential as an alternative approach for effective cancer treatment since it exerts minimal side effects on normal tissues. However, the photothermal stimulation increases the expression of heat shock protein (HSP) in tumor cells, rendering the tumor cells insensitive to heat and thus constraining the effects of PTT. In this study, biomimetic aggregation‐induced emission (AIE) photothermal agents with hitchhiking ability (DC@BPBBT dots) are developed by coating the nanoaggregates of the NIR AIE polymeric photothermal agents with dendritic cell (DC) membranes. Notably, the inner nanoaggregate (BPBBT dots) holds bright second‐window near infrared (NIR‐II) fluorescence (quantum yield of up to 3.47%) and a high photothermal conversion performance (photothermal conversion efficiency of up to 30.5%), and the outer cell membrane can facilitate the hitchhiking of DC@BPBBT dots on endogenous T cells and enhance the tumor delivery efficiency by about 1.2 times. Furthermore, DC@BPBBT dots can activate and stimulate T cells in vivo to secrete cytokine tumor necrosis factor α (TNF‐α), which can reduce the expression of heat shock protein 70 (HSP70) to render tumor cells more sensitive to heat. This study not only provides an alternative heat shock protein inhibition strategy based on immune cell interactions but also provides a hitchhike approach for drug delivery in cancer photothermal immunotherapy.

Photothermal Nanomaterials: A Powerful Light-to-Heat Converter

“…Since silica-cored Au nanoshells served as the first photothermal nanomaterials for clinical use, more and more inorganic agents with strong absorption in the NIR region, high chemical stability, adjustable water solubility, and minimal cytotoxicity have entered clinical trials. , Clinical trials have also been underway for small organic molecules due to their good biodegradability, good repeatability, and simple preparation. , Nevertheless, the major challenges for the clinical implementation of photothermal nanomaterials are the complex metabolism and excretion behaviors . The representative works on PTT with diverse photothermal nanomaterials in recent years − are summarized in Table .…”

Theranostic Nanoprobes with Aggregation‐Induced NIR‐II Emission: from Molecular Design to Biomedical Application

“…[71][72][73] In addition, the surface of NPs can be bioconjugated or chemically modified with some other functional groups to improve the targeting capability to tumors or other lesion locations (Figure 7A). [21,74] Moreover, recently developed automated millifluidic systems have realized large-scale production of NPs (up to 200 g day À 1 ) with uniform size and morphology based on NIR-II-emissive AIEgens, clearing a major obstacle for the clinical conversion and commercialization NIR-II-emissive AIEgens based NPs. [72,75] Another approach is chemically modifying the molecules with hydrophilic or amphiphilic chains to make the whole molecule amphiphilic for self-assembly (Figure 7A).…”

“…Recently, Protein, [78] cell membrane, [21,74,79] and liposomes [80] have also been developed to be used as natural packaging matrices for NPs preparation, usually in physical encapsulation, sometimes in chemical modification (Figure 7B and C). [80,81] These natural matrices can enhance the biosafety of obtained NPs.…”

“…For example, Gong and co-workers coated DC membranes onto OTPA-BBT (Figure 3) NPs, which enabled OTPA-BBT NPs to activate T cells for cytokines secretion and subsequent inhibition of HSPs in tumor cells. [21] In their another work, an amphipathic matrix with CO-release capacity when meeting H 2 O 2 (overexpressed in tumor site) was designed to encapsulate PBPTV (Figure 9) with a high PCE of 38.1 % to form NPs, which can release CO in the tumor microenvironment for HSPs inhibition. [20] Moreover, after HSPs being inhibited, the PTT could be realized at a relatively lower temperature, for example 42 ~43 °C, under which condition, the normal tissues would not be burned anymore, significantly reducing the side effects of PTT.…”

“…[18,19] Moreover, by being modified with functional groups, NPs can demonstrate special targeting capability with low biotoxicity. Some precise design could further endow the obtained NPs with special synergistic treatment [20][21][22] and fast metabolism capabilities. [23] In the NPs, the hydrophobic NIR-II fluorophores were in the aggregated state.…”