4.1.2. Polymer-Based Materials

Among the various template materials used to fabricate NP cores, polymer-based NPs have shown a series of technical advantages for carrier development. Such improvements in functional polymeric NPs for TCL delivery include the controllability of the sustained release of various TCL cargos, cargo-protective efficacy through encapsulation, increased half-life and bioavailability of antigens, and a compatibility with vaccine adjuvant delivery, which is beneficial for inducing long-lasting immunity [109].

Poly(lactic-co-glycolic acid) (PLGA) NPs have become a popular candidate for drug delivery systems due to their biodegradability via hydrolysis and easy surface functionalization [110,111], and they can also be used for the delivery of antigens or adjuvant to improve DC-mediated immune responses [112]. Table 2 summarizes the TCL delivery platforms using polymer-based materials.


**Table 2.** Polymer-based material delivery platforms for exogenous TCL delivery.

PLGA, poly(lactic-co-glycolic acid); TCL, tumor cell lysate; IL, interleukin; IFN, interferon; Th, T helper cell; CM, cell membrane; PEG, polyethylene glycol; R848, resiquimod; LN, lymph node; LM, liquid metal; CTS, chitosan; ROS, reactive oxygen species; PDA, polydopamine.

CTS Whole

PDA Whole

TCLs Mouse Mannose-coated

TCLs Mouse TCL-loaded PDA

The potential application of PLGA NPs loaded with gastric TCLs for antigastric tumor immunotherapy has been demonstrated [113]. In this instance, TCLs were prepared from primary gastric tumor cells obtained from gastric cancer patients, and encapsulated into PLGA NPs as DC antigen delivery vehicles. Upon delivery to mDCs, a higher expression of HLA-DR and co-stimulatory molecules (e.g., CD80 and CD86), and increased levels of IL-12 and IFN-γ were achieved than from bolus TCL treatment, leading to Th1 immune system pathway activation and augmented T lymphocyte proliferation. In addition to the conventional advantages of polymeric NPs for TCL delivery, PEGylation can also be applied to increase the retention time of therapeutic antigens, thus avoiding in vivo degradation by various proteases, and providing steric stabilization through the formation of a hydration layer on the particle surfaces [117]. Flexible PEG linker-mediated functionalization of NP surfaces also facilitates the adjustment of the chain length to improve cell recognition and uptake [118]. PEGlyated cancer cell membrane vesicles (PEG-CCVs) have also been developed to enhance serum stability and efficient trafficking to lymph nodes (Figure 4A) [26]. This PEGlyation was carried out using 5 kDa DSPE-PEG, and the resulting PEG-CCVs maintained in vitro stability (i.e., size and PDI) in 10% fetal bovine serum (FBS) conditions for 3 days at 37 ◦C, as well as in vivo draining efficiency to local lymph nodes upon subcutaneous administration. tumor immunotherapy has been demonstrated [113]. In this instance, TCLs were prepared from primary gastric tumor cells obtained from gastric cancer patients, and encapsulated into PLGA NPs as DC antigen delivery vehicles. Upon delivery to mDCs, a higher expression of HLA-DR and co-stimulatory molecules (e.g., CD80 and CD86), and increased levels of IL-12 and IFN-γ were achieved than from bolus TCL treatment, leading to Th1 immune system pathway activation and augmented T lymphocyte proliferation. In addition to the conventional advantages of polymeric NPs for TCL delivery, PEGylation can also be applied to increase the retention time of therapeutic antigens, thus avoiding in vivo degradation by various proteases, and providing steric stabilization through the formation of a hydration layer on the particle surfaces [117]. Flexible PEG linker-mediated functionalization of NP surfaces also facilitates the adjustment of the chain length to improve cell recognition and uptake [118]. PEGlyated cancer cell membrane vesicles (PEG-CCVs) have also been developed to enhance serum stability and efficient trafficking to lymph nodes (Figure 4A) [26]. This PEGlyation was carried out using 5 kDa DSPE-PEG, and the resulting PEG-CCVs maintained in vitro stability (i.e., size and PDI) in 10% fetal bovine serum (FBS) conditions for 3 days at 37 °C, as well as in vivo draining efficiency to local lymph nodes upon subcutaneous administration.

PLGA, poly(lactic-co-glycolic acid); TCL, tumor cell lysate; IL, interleukin; IFN, interferon; Th, T helper cell; CM, cell membrane; PEG, polyethylene glycol; R848, resiquimod; LN, lymph node; LM,

The potential application of PLGA NPs loaded with gastric TCLs for antigastric

Mitochondrial stress, ROS generation, and cGAS-STING pathway activation Improvement in NP uptake efficacy

Reacted with dopamine receptor

Increased the subpopulation of T cells [24]

[22]

*Pharmaceutics* **2022**, *14*, x FOR PEER REVIEW 12 of 26

Colorectal cancer

liquid metal; CTS, chitosan; ROS, reactive oxygen species; PDA, polydopamine.

TCLs-CTS NPs Melanoma

NPs

**Figure 4.** Schematic illustration of various biomaterial-based TCL delivery platforms. (**A**) PEGylated cancer cell membrane vesicles (CCVs) for steric stabilization, (**B**,**C**) PLGA nanoparticle-mediated delivery, (**D**) cancer cell membrane-coated inorganic material-based designs, (**E**) cell membranecoated liquid metal nanoparticle with NIR irradiation, (**F**,**G**) cargo encapsulated within liposomal nanoparticles with lipid-mediated surface modification (All figures were reproduced with permission from Refs. [26,114–116,119–121]).
