Rough Nanovaccines Boost Antitumor Immunity Through the Enhancement of Vaccination Cascade and Immunogenic Cell Death Induction

Abstract

Nanovaccines have attracted intense interests for efficient antigen delivery and tumor‐specific immunity. It is challenging to develop a more efficient and personalized nanovaccine to maximize all steps of the vaccination cascade by exploiting the intrinsic properties of nanoparticles. Here, biodegradable nanohybrids (MP) composed of manganese oxide nanoparticles and cationic polymers are synthesized to load a model antigen ovalbumin to form MPO nanovaccines. More interestingly, MPO could serve as autologous nanovaccines for personalized tumor treatment taking advantage of in situ released tumor‐associated antigens induced by immunogenic cell death (ICD). The intrinsic properties of MP nanohybrids including morphology, size, surface charge, chemical, and immunoregulatory functions are fully exploited to enhance of all steps of the cascade and induce ICD. MP nanohybrids are designed to efficiently encapsulate antigens by cationic polymers, drain to lymph nodes by appropriate size, be internalized by dendritic cells (DCs) by rough morphology, induce DC maturation through cGAS‐STING pathway, and enhance lysosomal escape and antigen cross‐presentation through the “proton sponge effect”. The MPO nanovaccines are found to efficiently accumulate in lymph nodes and elicit robust specific T‐cell immune responses to inhibit the occurrence of ovalbumin‐expressing B16‐OVA melanoma. Furthermore, MPO demonstrate great potential to serve as personalized cancer vaccines through the generation of autologous antigen depot through ICD induction, activation of potent antitumor immunity, and reversal of immunosuppression. This work provides a facile strategy for the construction of personalized nanovaccines by exploiting the intrinsic properties of nanohybrids.

Hybrids of Polysaccharides and Inorganic Nanoparticles: From Morphological Design to Diverse Biomedical Applications

“…CD possesses a hydrophilic exterior and a hydrophobic cavity to host hydrophobic molecules including adamantane (Ad), ferrocene, azobenzene, and their derivatives, for molecular recognition and assembly constructions via host–guest interactions . Our group utilized the classic host–guest interactions between CD and Ad to successfully introduce polycationic CD-PGEA (two-armed ethanolamine-functionalized poly­(glycidyl-methacrylate) with one β-CD core) onto the surface of a variety of inorganic nanoparticles for gene delivery. ,,,− Low-toxic hydroxyl-rich polycation CD-PGEA developed by our group can not only work as gene carriers, but also act as gatekeepers to control drug release in response to endogenous or exogenous stimuli. ,,,, …”

“…In an attempt to take advantage of the superior rough morphology, our group constructed inorganic nanoparticles with rough surfaces and assembled CD-PGEA on the surface to fabricate rough nanohybrids. ,,, For example, rattle-structured heteronanoparticles composed of rough SiO 2 nanocapsules and in situ formed Au NR cores (AHP) were synthesized successfully through a “ship-in-a-bottle” approach (Figure e) . AHP as well as the smooth counterparts sm-AHP were functionalized with CD-PEGA for gene delivery.…”

“…Encouraged by the advantageous properties of rough nanohybrids, our group further developed rough polysaccharide–inorganic nanohybrids for cancer immunotherapy and cancer vaccines. , By further optimizing the composition and morphology, we proposed a facile strategy to construct yolk–shell nanohybrids (Fe 3 O 4 @C/MnO 2 -PGEA, FCMP, Figure h,i) . FCMP composed of Fe 3 O 4 and MnO 2 can not only deplete GSH to enhance the generation of hydroxyl radicals (·OH) via Fenton reaction for CDT, but also reprogram tumor-associated macrophages from protumorigenic M2 phenotype to antitumor M1 phenotype .…”

Immunogenic dead cells engineered by the sequential treatment of ultraviolet irradiation/cryo-shocking for lung-targeting delivery and tumor vaccination

“…Besides serving as a passive lung-targeting delivery vehicle owing to the cellular size, the UV-cryo cells could further strengthen the antigen uptake/presentation by APCs to elicit efficient immune responses as a cancer vaccine. [39][40][41][42][43][44] After differentially loading the antitumor drug 10-hydroxycamptothecin (HCPT) and immunologic adjuvant Quillaja saponin-21 (QS-21) via physical absorption and chemical conjugation, respectively, this system (HCPT&QS-21/ UV-Cryo cell) could realize the fast release of chemo-drugs in lung and a long retention of the immune adjuvant, achieving the synergistic efficacy between chemo-and immunotherapy.…”

Design and investigation of targeting agent orientation and density on nanoparticles for enhancing cellular uptake efficiency

“…[1][2][3][4] Compared with traditional chemotherapeutic drugs, which usually suffer from quick clearance from the bloodstream and exhibit high cytotoxicity towards normal tissues, nanoparticle carriers possess many unique characteristics, such as tunable size, facile surface functionalization, high drug loading and good biocompatibility. [5][6][7] To date, different kinds of nanoparticles have been employed in therapeutic studies, including liposomes, 8,9 polymeric nanoparticles, [10][11][12] silica nanoparticles, [13][14][15] metal or metal oxide nanoparticles, [16][17][18] etc. Recently, much effort has been devoted to designing targeting nanoparticles to enhance the targeting efficacy and improve the accumulation of nanoparticles at the desired location of disease.…”