Supramolecular Assembled Programmable Nanomedicine As In Situ Cancer Vaccine for Cancer Immunotherapy

Abstract

Using nanotechnology for improving the immunotherapy efficiency represents a major research interest in recent years. However, there are paradoxes and obstacles in using a single nanoparticle to fulfill all the requirements in the complicated immune activation processes. Herein, a supramolecular assembled programmable immune activation nanomedicine (PIAN) for sequentially finishing multiple steps after intravenous injection and eliciting robust antitumor immunity in situ is reported. The programmable nanomedicine is constructed by supramolecular assembly via host–guest interactions between poly‐[(N‐2‐hydroxyethyl)‐aspartamide]‐Pt(IV)/β‐cyclodextrin (PPCD), CpG/polyamidoamine‐thioketal‐adamantane (CpG/PAMAM‐TK‐Ad), and methoxy poly(ethylene glycol)‐thioketal‐adamantane (mPEG‐TK‐Ad). After intravenous injection and accumulation at the tumor site, the high level of reactive oxygen species in the tumor microenvironment promotes PIAN dissociation and the release of PPCD (mediating tumor cell killing and antigen release) and CpG/PAMAM (mediating antigen capturing and transferring to the tumor‐draining lymph nodes). This results in antigen‐presenting cell activation, antigen presentation, and robust antitumor immune responses. In combination with anti‐PD‐L1 antibody, the PIAN cures 40% of mice in a colorectal cancer model. This PIAN provides a new framework for designing programmable nanomedicine as in situ cancer vaccine for cancer immunotherapy.

pH and lipase-responsive nanocarrier-mediated dual drug delivery system to treat periodontitis in diabetic rats

“…Many studies reported that Poly (amidoamine) (PAMAM) is pH-sensitive because of its loose structure under weakly acidic conditions [ 32 , 33 ], which could be exploited to trigger drug release, and thus could be widely used for responsive release in acidic environments. In addition, PAMAM is an excellent nanosized platform for drug delivery in numerous applications [ [34] , [35] , [36] ] because of its specific structure, such as the interior hydrophobic region, a large number of end amino groups, and narrow size distribution [ [37] , [38] , [39] , [40] , [41] ]. Moreover, many bacterial enzymes (e.g., esterase, lipase, and gelatinase) exist in dental plaque [ 29 , 42 , 43 ] and can be exploited to achieve enzyme-mediated drug release.…”

Emerging vaccine nanotechnology: From defense against infection to sniping cancer

“…Natural killer (NK) cell membrane 119 and myeloid-derived suppressor cell membrane 174 are useful to coat nanoparticles for enhanced PDT to promote ICD and activate immune responses that suppress significantly both in situ and metastatic tumors. In situ immunotherapy requires multiple steps, to address this issue, a recent study reported a nanomedicine strategy for programmable immune activation driven by the high level of reactive oxygen species induced by supramolecular assembled nanoparticle in the tumor microenvironment 175 . Release of drug and CpG/PAMAM led to the exposure of tumor antigen and APC activation, and subsequent antitumor immune responses.…”

Homotypic targeting of immunomodulatory nanoparticles for enhanced peripheral and central immunity

“… 7 , 8 , 9 Synthetic oligodeoxynucleotides (ODNs) comprised CpG motifs are found to stimulate similar immunomodulatory responses and display a great potential in the therapy of infection, cancer, or allergy. 5 , 10 , 11 However, free CpG ODNs are susceptible to nuclease cleavage and have poor cell permeability due to their anionic and hydrophilic properties. 12 , 13 , 14 , 15 , 16 Although phosphorothioate modification of the backbone can confer the resistance to nuclease degradation, it concurrently increases the cytotoxicity and thereby limits the clinical utilization of CpG ODNs.…”