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Interaction of the biomimetic nanomedicine with macrophages in vitro. a CLSM images of the RAW 264.7 macrophages treated with Cy5-labelled PG@KMCM (red). The cell membrane and the nuclei were stained by Dil (green) and DAPI (blue), respectively. The bars represent 20 μm. b Fluorescence intensity distribution patterns of the M1-like (blue) and M2-like (red) macrophages treated with FITC-labelled PG@KCM or PG@KMCM nanomedicine. c The corresponding mean FITC fluorescence intensities between the two macrophage subsets were compared. *p < 0.05, Student’s t test. d CLSM visulization of the M1-like and M2-like macrophages treated with Cy5-labelled (purple) PG@KCM or PG@KMCM. The nuclei were stained with DAPI (blue). The bars represent 50 μm. e Viability evaluation in the treated macrophage subsets by the LIVE/DEAD™ staining method. The alive and dead cells were stained in green and red, respectively. The bars represent 200 μm
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The therapeutic effect of chemotherapeutics such as gemcitabine against pancreatic cancer is considerably attenuated by immune-suppressive tumor microenvironment. Improvement of chemotherapeutic efficacy by targeting tumor-associated macrophage and reprograming tumor microenvironment to enhance their efficacy may become a promising strategy. To thi...
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Background: Improving the aggregation and penetration in tumor sites increases the anti-tumor efficacy of nanomedicine. In the current study, we designed cyclodextrin modified PLGA nanoparticles loaded with paclitaxel to elevate the accumulation and prolong circulation of chemotherapy drugs in vivo.
Methods: The PLGA nanoparticles loaded with pacli...
Citations
... Wang et al. 182 transfected pancreatic cancer KPC cells with lentivirus encoding M2pep, a peptide targeting M2 macrophages, and conrmed the presence of M2pep on KPC cell membranes by CLSM visualization. Then, M2pep-expressing KPC cell membranes (KMCM) were encapsulated on the surface of gemcitabine-loaded PLGA NPs, and biomimetic NPs (PG@KMCM) were synthesized for co-targeting of macrophages and tumors. ...
Nanoparticle (NP) drug delivery systems have shown promise in tumor therapy. However, limitations such as susceptibility to immune clearance and poor targeting in a complex intercellular environment still exist. Recently, cancer cell membrane-encapsulated nanoparticles (CCM-NPs) constructed using biomimetic nanotechnology have been developed to overcome these problems. Proteins on the membrane surface of cancer cells can provide a wide range of activities for CCM-NPs, including immune escape and homologous cell recognition properties. Meanwhile, the surface of the cancer cell membrane exhibits obvious antigen enrichment, so that CCM-NPs can transmit tumor-specific antigen, activate a downstream immune response, and produce an effective anti-tumor effect. In this review, we first provided an overview of the functions of cancer cell membranes and summarized the preparation techniques and characterization methods of CCM-NPs. Then, we focused on the application of CCM-NPs in tumor therapy. In addition, we summarized the functional modifications of cancer cell membranes and compiled the patent applications related to CCM-NPs in recent years. Finally, we proposed the future challenges and directions of this technology in order to provide guidance for researchers in this field.
... In both cell lines, the cytotoxic effects of DRT-DTX-PLGA were significantly higher than those of NT-DTX-PLGA and free DTX, indicating a substantial synergistic enhancement of intracellular uptake by the dual ligand nanoparticle system (Emami et al., 2023). Wang et al. (2022) had also developed dual-targeting nanoparticles known as PG@KMCM. The results showed that these nanoparticles could effectively reprogram the tumor microenvironment, killing pancreatic cancer cells and enhancing the overall therapeutic potential. ...
Cancer presents a formidable threat to human health, with the majority of cases currently lacking a complete cure. Frequently, chemotherapy drugs are required to impede its progression. However, these drugs frequently suffer from drawbacks such as poor selectivity, limited water solubility, low bioavailability, and a propensity for causing organ toxicity. Consequently, a concerted effort has been made to seek improved drug delivery systems. Nano-drug delivery systems based on biodegradable polyesters have emerged as a subject of widespread interest in this pursuit. Extensive research has demonstrated their potential for offering high bioavailability, effective encapsulation, controlled release, and minimal toxicity. Notably, poly (ε-caprolactone) (PCL), poly (lactic-co-glycolic acid) (PLGA), and polylactic acid (PLA) have gained prominence as the most widely utilized options as carriers of the nano drug delivery system. This paper comprehensively reviews recent research on these materials as nano-carriers for delivering chemotherapeutic drugs, summarizing their latest advancements, acknowledging their limitations, and forecasting future research directions.
... In addition, the inactivation of tumor infiltrating T cells is an important factor affecting the effect of immunotherapy [21]. Typically, tumor cells counteract immune cell clearance by upregulating PD-L1 expression [22,23], while also secreting exosomes to suppress naive T cell activation and effector T cell function [24,25]. Therefore, the commonly used strategy in combination therapy is the activation of tumor-specific effector T cells using tumor vaccines while also maintaining their antitumor capacity through an immune checkpoint blockade (ICB) strategy [26,27]. ...
Tumor vaccines trigger tumor-specific immune responses to prevent or treat tumors by activating the hosts’ immune systems, and therefore, these vaccines have potential clinical applications. However, the low immunogenicity of the tumor antigen itself and the low efficiency of the vaccine delivery system hinder the efficacy of tumor vaccines that cannot produce high-efficiency and long-lasting antitumor immune effects. Here, we constructed a nanovaccine by integrating CD47KO/CRT dual-bioengineered B16F10 cancer cell membranes and the unmethylated cytosine-phosphate-guanine (CpG) adjuvant. Hyperbranched PEI25k was used to load unmethylated cytosine-phosphate-guanine (CpG) through electrostatic adsorption to prepare PEI25k/CpG nanoparticles (PEI25k/CpG-NPs). CD47KO/CRT dual-bioengineered cells were obtained by CRISPR-Cas9 gene editing technology, followed by the cell surface translocation of calreticulin (CRT) to induce immunogenic cell death (ICD) in vitro. Finally, the extracted cell membranes were coextruded with PEI25k/CpG-NPs to construct the CD47KO/CRT dual-bioengineered cancer cell membrane-coated nanoparticles ([email protected]). [email protected] could promote endocytosis of antigens and adjuvants in murine bone marrow derived dendritic cells (BMDCs) and induce their maturation and antigen cross-presentation. To avoid immune checkpoint molecule-induced T cell dysfunction, the immune checkpoint inhibitor, the anti-PD-L1 antibody, was introduced to boost tumor immunotherapy through a combination with the [email protected] nanovaccine. This combination therapy strategy can significantly alleviate tumor growth and may open up a potential strategy for clinical tumor immunotherapy.
... GEM was loaded into the cavity of self-assembled chemically modified PAMAM dendrimer NPs (120 nm) that degrade at tumor tissue into small particles (10 nm), which facilitated deep tumor penetration in 3D multicellular spheroids. 53 The NPs also increased infiltration of cytotoxic CD8 + T cells and a remarkable decrease in MDSC, TAMs, and Tregs, thus improving the therapeutic efficacy of PD-1 antibodies against Panc02 tumors in mice. Further progress has engineered PC cells to express TAAs (for targeting PC cells) and M2pep (for targeting M2-TAMs) on their membranes. ...
Pancreatic cancer (PC) is a highly aggressive malignant type of cancer. Although immunotherapy has been successfully used for treatment of many cancer types, many challenges limit its success in PC. Therefore, nanomedicines were engineered to enhance the responsiveness of PC cells to immune checkpoint inhibitors (ICIs). In this review, we highlight recent advances in engineering nanomedicines to overcome PC immune resistance. Nanomedicines were used to increase the immunogenicity of PC cells, inactivate stromal cancer-associated fibroblasts (CAFs), enhance the antigen-presenting capacity of dendritic cells (DCs), reverse the highly immunosuppressive nature of the tumor microenvironment (TME), and, hence, improve the infiltration of cytotoxic T lymphocytes (CTLs), resulting in efficient antitumor immune responses.
... Nano-formation enables the simultaneous targeted delivery of gemcitabine to the pancreatic tumor sites and TAMs repolarization to potentiate its therapeutic effects. This nano-formation also synergistically enhances the antitumor effect of PD-L1 antibodies in the PDAC [100]. ...
Immunotherapy has dramatically changed prognosis for patients with malignant tumors. However, as a non-immunogenic tumor, pancreatic ductal adenocarcinoma (PDAC) has a low response to immunotherapy. Factors that contribute to the inefficiency of PDAC immunotherapy include the tumor microenvironment (TME) and its dense stroma, which acts as a barrier for drug delivery and immune cell infiltration. Recent studies have shown that nanoparticle-based therapeutic strategies have more promising applications in improving drug delivery and reversing the immunosuppressive TME for PDAC. Therefore, nanomaterial-based therapeutic approaches are expected to enhance the effectiveness of immunotherapy and improve prognosis of patients with PDAC. Here, we outline the status and dilemma of PDAC immunotherapy, and summarize the latest advances in nanoparticle-based treatment strategies to enhance the efficacy of PDAC immunotherapy.
... The immunotherapy was potentiated by synergetic activated IRF5 and the NF-κB signaling pathway by Fe 3 O 4 and imiquimod, respectively . Recently, bioengineered CCM that overexpresses peptides targeting M2 macrophages guided the notion of 'one stone (gemcitabine) kill two birds (both cancer cells and TAMs)' (Wang et al., 2022a). Indeed, the CM-based bionic platform is high profile for enhanced antigen or adjuvant delivery as well as macrophage polarization in TME. ...
The emerging cell membrane (CM)-camouflaged poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) (CM@PLGA NPs) have witnessed tremendous developments since coming to the limelight. Donning a novel membrane coat on traditional PLGA carriers enables combining the strengths of PLGA with cell-like behavior, including inherently interacting with the surrounding environment. Thereby, the in vivo defects of PLGA (such as drug leakage and poor specific distribution) can be overcome, its therapeutic potential can be amplified, and additional novel functions beyond drug delivery can be conferred. To elucidate the development and promote the clinical transformation of CM@PLGA NPs, the commonly used anucleate and eukaryotic CMs have been described first. Then, CM engineering strategies, such as genetic and nongenetic engineering methods and hybrid membrane technology, have been discussed. The reviewed CM engineering technologies are expected to enrich the functions of CM@PLGA for diverse therapeutic purposes. Third, this article highlights the therapeutic and diagnostic applications and action mechanisms of PLGA biomimetic systems for cancer, cardiovascular diseases, virus infection, and eye diseases. Finally, future expectations and challenges are spotlighted in the concept of translational medicine.
Pancreatic cancer is an aggressive and highly fatal malignant tumor. Recent studies have shown that cancer stem cells (CSCs) play an important role in resisting current therapeutic modalities. Furthermore, CD133 is highly expressed in CSCs. High-intensity focused ultrasound (HIFU) is a promising non-invasive therapeutic strategy for unresectable pancreatic cancers. In our study, we synthesized targeted CD133 organosilane nanomicelles by encapsulating perfluorohexane (PFH). The CD133 antibody on the surface could specifically bind to CD133-positive pancreatic cancer cells and selectively concentrate in pancreatic cancer tumor tissues. PFH was introduced to improve the ablation effect of HIFU due to its liquid-gas phase transition properties. By combining with the dorsal skinfold window chamber model (DSWC) of pancreatic cancer in nude mice, multiphoton fluorescence microscopy was used to evaluate the targeting effect of nanomicelles on pancreatic cancer tumor tissue. These multifunctional nanomicelles synergistically affected HIFU treatment of pancreatic cancer, providing an integrated research platform for diagnosing and treating pancreatic cancer with HIFU.
Nanovaccines have gathered significant attention for their potential to elicit tumor-specific immunological responses. Despite notable progress in tumor immunotherapy, nanovaccines still encounter considerable challenges such as low delivery efficiency, limited targeting ability, and suboptimal efficacy. With an aim of addressing these issues, engineering customized nanovaccines through modification or functionalization has emerged as a promising approach. These tailored nanovaccines not only enhance antigen presentation, but also effectively modulate immunosuppression within the tumor microenvironment. Specifically, they are distinguished by their diverse sizes, shapes, charges, structures, and unique physicochemical properties, along with targeting ligands. These features of nanovaccines facilitate lymph node accumulation and activation/regulation of immune cells. This overview of bespoke nanovaccines underscores their potential in both prophylactic and therapeutic applications, offering insights into their future development and role in cancer immunotherapy.
