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Application of Carbon Nanotubes in Cancer Vaccines as Drug Delivery Tools
Published in Loutfy H. Madkour, Nanoparticle-Based Drug Delivery in Cancer Treatment, 2022
In 2014, Faria et al. have reported the delivery of antigen and adjuvant to APCs using CNTs [135]. In this study, the model antigen OVA and the TLR9 agonist CpG were both noncovalently linked to carboxylate MWNTs. Mice immunized with MWNT-conjugated OVA and CpG showed higher sera levels of anti-OVA IgG and IFNγ production by ex vivo stimulated splenocytes than mice immunized with free OVA and CpG. The authors also tested the ability of the carboxylated MWNTs to co-deliver NY-ESO-1 (tumor antigen expressed in various human cancers) in combination with CpG to the APCs. The immune response induced in vivo by NY-ESO-1 and CpG was intensified following their noncovalent linkage to MWNTs. In addition, testing the ability to induce protective immunity, mice pre-injected with NY-ESO-1 and CpG-loaded MWNTs demonstrated a markedly retarded growth of NY-ESO-1 expressing B16F10 melanoma cells in subcutaneous tumor model. However, to assess the therapeutic efficacy of the designed MWNT-based vaccine, tumor-inoculated mice were vaccinated three days post-tumor cell inoculation, when tumor growth was still undetectable. Therefore, it is unclear whether therapeutic vaccination with carboxylate MWNTs co-delivering antigen in combination with CpG ODN would lead to effective remission of a well-established tumor.
Immunological response of polysaccharide nanogel-incorporating PEG hydrogels in an in vivo diabetic model
Published in Journal of Biomaterials Science, Polymer Edition, 2022
Tugba Bal, Ismail Can Karaoglu, Fusun Sevval Murat, Esra Yalcin, Yoshihiro Sasaki, Kazunari Akiyoshi, Seda Kizilel
Hydrogel nanoparticles, referred as nanogels, are either physically or chemically crosslinked polymer networks with sizes less than 100 nm in diameter. Chemically crosslinked nanogels are formed by covalent bonds whereas physically crosslinked nanogels are established by non-covalent bonds such as electrostatic and hydrophobic interactions [17]. To achieve physical crosslinking, self-assembly method based on hydrophobic interactions can be used and it is an effective approach to synthesize nanogels [18]. Polymer systems containing both hydrophobic and hydrophilic groups in their structure are promising due to the simultaneous employment of non-covalent pi stackings and solubility in aqueous media [19]. Pullulan is a hydrophilic polysaccharide produced from the fungal fermentation of starch. Being biodegradable, non-toxic, non-immunogenic and FDA-approved, pullulan is a commonly used natural polymer in fields such as pharmaceutical, cosmetics and biomedical [20,21]. Moreover, pullulan has a good adhesive property, and it is reported to enhance MSC retention on injured cartilage tissue by providing a reparative environment [22]. Repeating groups of pullulan consist of maltotriose units which are suitable for functionalization with various molecules [23]. Among these molecules, functionalization of pullulan with cholesterol have attracted great attention in recent decades for the synthesis of nano and microstructures [24–28]. Cholesterol-bearing and acryloyl modified pullulan (CHPOA) nanogels are composed of hydrophilic structures of pullulan and hydrophobic cholesteryl groups. In aqueous media, aforementioned hydrophobic moieties of CHPOA are responsible for physical crosslinking [29]. Additionally, CHPOA nanogels have been reported to lack stimulatory molecules, which makes them immunologically inert [16,30]. Therefore, they have attracted attention to be tested in clinics. For instance, as a part of cancer vaccine, these nanoparticles were utilized to deliver NY-ESO-1 that evokes and facilitates T-cell response [31]. In a calvarial defect model, CHPOA nanogels were shown to enhance osteoprogenitor cell infiltration by releasing fibroblast growth factor-18 and bone morphogenic protein-2, resulting in fast recovery [32].