Biodegradable Mesoporous Silica Achieved via Carbon Nanodots-Incorporated Framework Swelling for Debris-Mediated Photothermal Synergistic Immunotherapy

Abstract

Incorporating carbon nanodots (CDs) into mesoporous silica framework for extensive biomedicine, especially for the desirable cancer immunotherapy, is considered to be an unexplored challenge. Herein, a hydrogen bond/electrostatic-assisted co-assembly strategy was smartly exploited to uniformly incorporate polymer-coated CDs into ordered framework of mesoporous silica nanoparticles (CD@ MSNs). The obtained CD@MSN was not only biodegradable via the framework-incorporated CD-induced swelling but also capable of gathering dispersive CDs with enhanced photothermal effect and elevated targeting accumulation, which therefore can achieve photothermal imaging-guided photothermal therapy (PTT) in vitro and in vivo. Interestingly, benefiting from the biodegraded debris, it was found that CD@MSN-mediated PTT can synergistically achieve immunemediated inhibition of tumor metastasis via stimulating the proliferation and activation of natural killer cells and macrophages with simultaneously up-regulating the secretion of corresponding cytokines (IFN-γ and Granzyme B). This work proposed an unusual synthesis of biodegradable mesoporous silica and provided an innovative insight into the biodegradable nanoparticlesassociated anticancer immunity.

The Coppery Age: Copper (Cu)‐Involved Nanotheranostics

“…The rational integration of PTT and immunotherapy not only inhibits the primary tumor growth but also suppresses the distant tumor growth by activating the host antitumor immunity. [ 208–212 ] For instance, chitosan‐coated hollow CuS nanoparticles assembled with immunoadjuvants oligodeoxynucleotides containing the cytosine‐guanine (CpG) motifs for synergistic photothermal immunotherapy against breast cancer on mouse model. [ 213 ] The typical photothermal effect of CuS component not only inhibited the primary tumor growth, but also released the tumor antigens, and the immunoadjuvants initiated the host antitumor immunity to suppress the distant untreated tumor growth.…”

Engineering nanomedicines through boosting immunogenic cell death for improved cancer immunotherapy

“…The hyperthermic effect induced by PTT destroys tumor cells by disrupting the cell membrane, denaturing proteins and inducing DNA damage [ 57 ]. In addition, PTT induces immune responses by releasing TAAs and other immunostimulatory molecules [ 58 , 59 ]. To take advantage of PTT-induced ICD, Prussian blue nanoparticles combined with PTT administered at temperatures between 63.3 and 66.4 °C induced a robust ICD-mediated antitumor effect and long-term survival in a neuroblastoma tumor model [ 60 ].…”

Electromagnetic Nanomedicines for Combinational Cancer Immunotherapy

“…The M1‐type macrophages that had been repolarized by iron ions could capture, process, and present TAAs released by PTT through the major histocompatibility complex class II pathway, increasing the infiltration of CD4 + and CD8 + T cells in tumor sites, which led to inhibited tumor growth and metastasis of 4T1 tumors. Huang and colleagues constructed a biodegradable carbon nanodot‐incorporated mesoporous silica NP for synergistic PTT–immunotherapy [75] . The formed NP could degrade into nanodebris as a result of the swelling induced by the carbon nanodots incorporated in the framework.…”