Abstract
BackgroundTherapeutic tumor vaccine (TTV) that induces tumor-specific immunity has enormous potentials in tumor treatment, but high heterogeneity and poor immunogenicity of tumor seriously impair its clinical efficacy. Herein, a novel NIR responsive tumor vaccine in situ (HA-PDA@IQ/DOX HG) was prepared by integrating hyaluronic acid functionalized polydopamine nanoparticles (HA-PDA NPs) with immune adjuvants (Imiquimod, IQ) and doxorubicin (DOX) into thermal-sensitive hydrogel.ResultsHA-PDA@IQ NPs with high photothermal conversion efficiency (41.2%) and T1-relaxation efficiency were using HA as stabilizer by the one-pot oxidative polymerization. Then, HA-PDA@IQ loaded DOX via π-π stacking and mixed with thermal-sensitive hydrogel to form the HA-PDA@IQ/DOX HG. The hydrogel-confined delivery mode endowed HA-PDA@IQ/DOX NPs with multiple photothermal ablation performance once injection upon NIR irradiation due to the prolonged retention in tumor site. More importantly, this mode enabled HA-PDA@IQ/DOX NPs to promote the DC maturation, memory T cells in lymphatic node as well as cytotoxic T lymphocytes in spleen.ConclusionTaken together, the HA-PDA@IQ/DOX HG could be served as a theranostic tumor vaccine for complete photothermal ablation to trigger robust antitumor immune responses.
Highlights
Therapeutic cancer vaccine (TCV) that aims to stimulate tumor antigen-specific immunological responses is emerging as promising technology in cancer immunotherapy in recent years [1,2,3]
In this study, we reported that a novel near infrared (NIR) responsive nanovaccine (HA-PDA@IQ/DOX HG) for in situ photothermal ablation (PTA) and chemotherapy can boost anti-tumor immunity
hyaluronic acid (HA) was used as template molecule to encapsulate IQ and assist dopamine oxidative polymerization catalyzed by potassium permanganate
Summary
Preparation and characterization of HA‐PDA@IQ/DOX NPs As shown in Scheme 1, HA-PDA@IQ NPs were synthesized by the one-pot self-polymerization of dopamine initiated by K MnO4 in the presence of stabilizer (HA) and immune adjuvant (IQ). The tumor cells 4T1 and normal cell MEF were co-cultured with different concentrations of HA-PDA@IQ NPs and irradiated with 808 nm laser for 5 min (2 W/cm2) The PTA performance of HA‐PDA@IQ/DOX HG in vivo In order to evaluate the photothermal performance in vivo, digital NIR thermal imager was chosen to realtime monitor temperature profile of tumor site after in situ injection of HA-PDA@ IQ/DOX HG.
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