Nanomedicines combining multimodal therapeutic modalities supply opportunities to eliminate
tumors in a safe and efficient manner. However, the rigid encapsulation and covalent conjugation of different therapeutic
reagents suffer from the complicated preparation process, premature drug leakage and severe adverse events. Herein, we report a self-enhanced supramolecular nanomedicine (SND) based on the host-guest molecular recognition between β-
cyclodextrin (β-CD) and
camptothecin (
CPT) for trimodal synergistic
chemotherapy,
photodynamic therapy (
PDT) and
photothermal therapy (PTT) using a single 670 nm near-infrared (NIR)
laser. Thioketal bond and
polyethylene glycol (PEG) segment are introduced into the structure of
CPT-tk-PEG
prodrug, thus the premature release of
CPT is efficiently inhibited and the specific drug release is realized at
tumor site where
singlet oxygen (1O2)-generated
PDT is performed. A
boron dipyrromethene (
BODIPY)
theranostic agent is anchored onto β-CD, endowing SND with capabilities of fluorescence imaging,
PDT and PTT. Benefiting from the supramolecular assembly, not only the solubility of
CPT is improved by 40 times, but also the blood circulation time and
tumor accumulation of SND are greatly promoted. In vivo, SND can effectively induce the immunogenic cell death (ICD) of
tumor cells, thus performing prominent inhibition against both primary and distal
tumors, and even anti-
metastasis effect against liver without causing obvious systemic toxicity. STATEMENT OF SIGNIFICANCE: Although nanomedicines supply opportunities to eliminate
tumors in an efficient manner, they usually suffer from premature drug leakage, complicated preparation process and severe side effects owing to the rigid encapsulation or covalent conjugation. Based on the host-guest molecular recognition, we developed a self-enhanced SND for synergistic
chemotherapy,
photodynamic therapy and
photothermal therapy. Introduction of thioketal bond in
CPT prodrug avoided the premature drug release, and the specific drug release was realized in the
tumor cells. Profiting from the facile supramolecular assembly strategy, SND not only displayed a primary anticancer efficacy with a low systemic toxicity, but also efficiently inhibited the growth of distal
tumors, contributing a
vaccine-like function to eradicate the recurrent and metastatic
tumors.