Biologically Responsive Plasmonic Assemblies for Second Near-Infrared Window Photoacoustic Imaging-Guided Concurrent Chemo-Immunotherapy

Abstract

We developed dual biologically responsive nanogapped gold nanoparticle vesicles loaded with immune inhibitor and carrying an anticancer polymeric prodrug for synergistic concurrent chemo-immunotherapy against primary and metastatic tumors, along with guided cargo release by photoacoustic (PA) imaging in the second near-infrared (NIR-II) window. The responsive vesicle was prepared by self-assembly of nanogapped gold nanoparticles (AuNNPs) grafted with poly­(ethylene glycol) (PEG) and dual pH/GSH-responsive polyprodug poly­(SN38-co-4-vinylpyridine) (termed AuNNP@PEG/PSN38VP), showing intense PA signal in the NIR-II window. The effect of the rigidity of hydrophobic polymer PSN38VP on the assembled structures and the formation mechanism of AuNNP@SN38 Ve were elucidated by computational simulations. The immune inhibitor BLZ-945 was encapsulated into the vesicles, resulting in pH-responsive release of BLZ-945 for targeted immunotherapy, followed by the dissociation of the vesicles into single AuNNP@PEG/PSN38VP. The hydrophilic AuNNP@PEG/PSN38VP nanoparticles could penetrate deep into the tumor tissues and release the anticancer drug SN38 under the reductive environment. A PA signal in the NIR-II window in the deep tumor region was obtained. The BLZ-945-loaded vesicle enabled enhanced PA imaging-guided concurrent chemo-immunotherapy efficacy, inhibiting the growth of both primary tumors and metastatic tumors.

Responsive Polymer Brush Design and Emerging Applications for Nanotheranostics

“…The modified AuNNPs further self‐assembled into a nanocomplexed vesicles and loaded with small molecular immune inhibitor 4‐[[2‐[[(1R,2R)‐2‐hydroxycyclohexyl]amino]‐6‐benzothiazolyl]oxy]‐ N ‐methyl‐2‐pyridinecarboxamide (BLZ‐945) (AuNNP@SN 38 /BLZ‐945) to enable imaging‐guided chemo‐immunotherapy. [ 113 ] At low pH, BLZ‐945 targeting tumor‐associated macrophages were decomposed by these responsive AuNNP@SN 38 /BLZ‐945 vesicles, followed by deep penetration of AuNNPs@SN 38 into the tumor. Within the reductive tumor microenvironment, SN 38 was released to induce cancer cell apoptosis.…”

Smart materials for drug delivery and cancer therapy

“…Many exogenous response materials that were sensitive to temperature, light, radiation, ultrasound, and magnetic, as mentioned above, were combined with endogenous sensitive smart materials for cooperative action of chemotherapy and PDT/PTT, 46,119,285 controlled multistage drug delivery, 286–290 cooperative action of chemotherapy and SDT, 291 sequentially triggered excellent RT, 292 PAI‐guided synergistic chemo‐PTT, 156,290 MRI‐guided combinatorial chemotherapy, 95,120,121 etc. In a typical example, a pH‐/thermal‐/GSH‐responsive polymer zipper was engineered as the smart surface of nanocarriers 289 .…”

“…At last, endogenous GSH could digest the RGD‐tailed poly(disulfide)s bearing Gu + residues and collapse the zipper with drug release. Moreover, in another recent study, Zhu et al developed the PAI‐guided concurrent chemo‐immunotherapy system by the self‐assembled PEG‐grafted nanogapped gold nanoparticles (AuNNPs) and poly(SN38‐co‐4‐vinylpyridine) (a dual pH/GSH‐responsive polyprodrug) 290 . The AuNNPs encapsulated immune inhibitor BLZ‐945 to achieve targeted pH‐responsive immunotherapy.…”

Recent advances in applications of multimodal ultrasound-guided photoacoustic imaging technology

“…relatively stronger PA signals for SPNs3 were detected in the tumor region compared with those in the untreated group and the SPNs2-treated group, implying that SPNs3 is an available PA agent in the NIR-II window. In 2020, Zhu et al [23] developed dual biologically responsive nanogapped gold nanoparticle (Au NPs) vesicles loaded with immune inhibitors and carried anticancer polymeric prodrugs for synergistic concurrent chemoimmunotherapy against primary and metastatic tumors, along with guided cargo release by PAI in the NIR-II window (Fig. 5).…”

“…The smaller AuNNP@PEG/PSN 38 VP then penetrated the deeper tumor regions and released the SN 38 prodrug in the reductive environment, leading to tumor cell apoptosis. PA imaging in the NIR-II window further enabled drug release monitoring and guided therapy[23] MRI and PAI performance in vivo[25] Wang et al Visual Computing for Industry, Biomedicine, and Art (2020) 3:24the excellent photothermal conversion capability under NIR irradiation to show a squaraine dye (SQ1) nanoprobe that performed well in both PAI and PTT of solid tumors. These results indicate that SQ1 nanoprobes have significant tumor targeting imaging capabilities.…”