Biopolymer–Drug Conjugate Nanotheranostics for Multimodal Imaging-Guided Synergistic Cancer Photothermal–Chemotherapy

Some of the biomedical polymer–drug conjugates are being translated into clinical trials; however, they intrinsically lack photothermal and multi-imaging capabilities, hindering them from imaging-guided precision cancer therapy and complete tumor regression. We introduce a new concept of all-in-one biopolymer–drug conjugate nanotheranostics and prepare a kind of intracellular pH-sensitive polydopamine–doxorubicin (DOX) conjugate nanoparticles (PDCNs) under mild conditions. Significantly, this strategy integrates polymeric prodrug-induced chemotherapy (CT), near-infrared (NIR) light-mediated photothermal therapy (PT), and triple modalities including DOX self-fluorescence, photothermal, and photoacoustic (PA) imaging into one conjugate nanoparticle. The PDCNs present excellent photothermal property, dual stimuli-triggered drug release behavior, and about 12.4-fold blood circulation time compared to free DOX. Small animal fluorescent imaging technique confirms that PDCNs have preferential tumor accumulation effect in vivo, giving a 12.8-fold DOX higher than the control at 12 h postinjection. Upon NIR laser irradiation (5 min, 808 nm, and 2 W·cm –2 ), the PDCN-mediated photothermal effect can quickly elevate the tumor over 50 °C, exhibiting good photothermal and PA imaging functions, of which the PA amplitude is 3.6-fold greater than the control. In vitro and in vivo assays persuasively verify that intravenous photothermal–CT of PDCNs produces synergistic antitumor activity compared to single PT or CT, achieving complete tumor ablation during the evaluation period.