Every entry summarises what the study set out to test, what it found and why it changes how we design delivery systems. Browse research and reviews or search the collection.
Yue Wang, Shi-Kun Zhou, Yan Wang, Zi-Dong Lu, Yue Zhang, Cong-Fei Xu, Jun Wang
PD-1/PD-L1 blockade therapy is successful but often yields poor benefits due to insufficient T-cell infiltration and low intratumoral concentrations of PD-1/PD-L1 inhibitors. While strategies exist to increase either T-cell recruitment or inhibitor delivery, none actively recruit T cells while achieving tumor-specific delivery of PD-L1 inhibitors to specifically eliminate inhibition of tumor-infiltrating T cells. A strategy that addresses both. ### Nanoparticle Characterization | Parameter | Value | |---------------|-----------| | Hydrodynamic diameter | 107.2 nm | | PDI | ~0.2 | | Zeta potential | +15.3 mV | | Stability in 10% FBS | ≥5 days (size/PDI stable).
Yingping Zeng, Sufen Li, Shufen Zhang, Li Wang, Hong Yuan, Fuqiang Hu
Cancer immunotherapy is limited by tumor heterogeneity, immune cell disability, immunosuppressive tumor microenvironment (TME), and systemic immune toxicity. Cell membrane-coated nanoparticles (CMCNs) offer a biomimetic delivery strategy that inherits source-cell functions—immune evasion, tumor targeting, and biological compatibility—to precisely deliver immunotherapeutic drugs and enhance anti-cancer immunity. --- - Cancer vaccine response rates: clinical patient response to cancer vaccines remains relatively low at 11–50%; ICB inhibitors show ~80% effective rate in lymphoma but only 10–30% in solid tumors. - Sipuleucel-T (Provenge) extends overall survival by 4.1 months in metastatic castration-resistant prostate cancer. - APMC vaccine (B16F10 cancer cell membrane-coated CpG/aluminum phosphate nanoparticles): increased DC maturation, enhanced cellular/humoral immunity, improved tumor prevention/treatment and longer mouse survival vs.
Rasheid Smith, Emad I. Wafa, Sean M. Geary, Kareem Ebeid, Suhaila O. Alhaj-Suliman, Aliasger K. Salem
Cancer vaccines as monotherapies have displayed limited clinical success due to the immunosuppressive tumor microenvironment (TME). Nanoscale formulations can enhance vaccine efficacy by combating TME immunosuppression, but there is a need for novel adjuvant formulations that can be combined with therapeutic cancer vaccines to improve antitumor immune responses and survival. ### Nanoparticle Characterization & Uptake | Parameter | PMG3 | PMG4 | PMG5 | |---------------|----------|----------|----------| | Hydrodynamic diameter | 231.7 ± 2.4 nm | 172.4 ± 3.0 nm | ~170 nm | | Zeta potential |.
Conventional chemotherapy suffers from poor targeting and severe side effects, while synthetic nanocarriers are often cleared by the immune system and lack precise tumor targeting. Cell membrane-coated nanocarriers (CMCNs) offer a biomimetic strategy to improve biocompatibility, immune evasion, circulation time, and homotypic tumor targeting. RBC membrane-coated PLGA nanocarriers improved blood retention to 72 hours vs 15.8 hours for typical PEGylated stealth nanocarriers. - Neutrophil membrane-coated nanocarriers showed 2–3-fold higher accumulation in.
Cancer immunotherapy — especially immune checkpoint inhibitors (ICIs), CAR-T cells, and oncolytic viruses (OVs) — has shown major clinical success but still faces low response rates, severe immune-related side effects, complex tumor microenvironment barriers, instability/short half-life of therapeutics, and high manufacturing costs. Polymeric systems are proposed as versatile carriers and immune-modulating platforms to improve targeting, safety. Representative findings highlighted in the review: - ICI delivery: Folate-PEI/PD-L1 siRNA blocked PD-1/PD-L1 interactions and reduced PEI cytotoxicity in ovarian cancer cells. PLGA-PEG nanoparticles targeted to CD8⁺ T.
Sureshbabu Ram Kumar Pandian, Clayton Fernando Rencllin, Krishnan Sundar
Conventional cancer immunotherapies (checkpoint inhibitors, CAR T cells) are effective but expensive, cause adverse side effects, and face challenges in solid tumours. Nanomaterials offer advantages in delivery, diagnostics, and immune modulation, but a comprehensive understanding of how different nanomaterial types (organic, inorganic, cell membrane-based) can be integrated into cancer immunotherapy—and how their biodistribution and toxicity profiles affect clinical translation—remains needed. --- - Cationic liposomes with α-GalCer and TRP2: Enhanced IFN-γ secretion, cytotoxic T-cell activation, and reduced tumour survival; PEG-coating reduced cytotoxicity. - PLGA nanoparticles with TLR ligands and antigen: Improved antibody and T-cell responses compared to soluble antigen plus adjuvants, resembling live viral vaccine immunogenicity. - Pyruvate dehydrogenase E2 nanoparticles with CpG and gp100: 1.5-fold increase in CD8+ T cells and 5-f
Tresa Lopez-Royo, Victor Sebastian, Laura Moreno-Martinez, Laura Uson, Cristina Yus, Teresa Alejo, Pilar Zaragoza, Rosario Osta, Manuel Arruebo, Raquel Manzano
CRISPR/Cas gene-editing components are often encoded on large plasmids (9–19 kb), which are difficult to encapsulate and transfect. Most PLGA nanoparticle (NP) gene-delivery studies use small nucleic acids (siRNA) or small plasmids (<6 kb), and the structural integrity and functional performance of large plasmids in PLGA NPs remain poorly characterized. There is a need to compare synthesis methods for encapsulating large plasmids without. pDNA stability: Batch ultrasound double emulsion completely degraded the 9.4 kb plasmid (standard) or left only 8.80% supercoiled (modified). Microfluidics-assisted double emulsion avoided degradation but produced only.
Jiayu Zhou, Yishu Zhai, Jumei Xu, Tian Zhou, Lian Cen
PLGA microspheres are widely used for controlled drug release, but they often exhibit pronounced initial or mid-term burst release. A strategy is needed to finely tune drug release kinetics and suppress burst release, especially for water-soluble drugs. MSNs: Average size 119 nm; specific surface area 902.53 m²/g; pore volume 1.15 cm³/g; mean pore diameter 5.09 nm; maximum RB loading ~110 mg/g. - MSN-RB release: ~95% cumulative release within 56 h; Korsmeyer–Peppas n =.
Julia Koerner, Dennis Horvath, Valerie L. Herrmann, Anna Mackeracher, Bruno Gander, Hideo Yagita, Jacques Rohayem, Marcus Groettrup
Cancer immunotherapy needs potent, pharmaceutically defined, GMP-compatible adjuvants for clinical translation. Poly(I:C) is a widely used TLR3 agonist but has ill-defined structure, heterogeneity, pyrogen contamination, and toxicity concerns. Riboxxim is a well-defined 100-bp double-stranded RNA with a 5′-triphosphate moiety that activates both endosomal TLR3 and cytosolic RIG-I. PLGA particles can co-deliver antigen and adjuvant to dendritic. Particle properties: MPs ~1–1.5 µm; NPs ~250 nm; negative zeta potential; OVA release burst within 24 h followed by sustained release. MPs showed better release profile than NPs. - Route comparison: Subcutaneous.
Nanomedicine translation is limited by non-scalable, batch-variable bulk NP formulation methods that often produce large, polydisperse particles. Microfluidics offers precise control over microscale mixing and nanoprecipitation, enabling more reproducible NPs with controlled size, size distribution, and loading. This review summarizes microfluidic advances for lipid-, polymer-, and inorganic-based NPs. Representative quantitative findings from reviewed literature: - SHM-produced LNPs: 60–90 nm vs ~180 nm by pipette mixing; >90% hepatic gene silencing; up to 7-fold increased mRNA potency. - Parallelized SHM: 72 mL/min;.
Gong N, Sheppard Nc, Billingsley Mm, June Ch, Mitchell Mj.
T-cell-based immunotherapies have shown clinical success in B-cell malignancies, but broad implementation is limited by insufficient T-cell expansion, poor trafficking into solid tumours, T-cell exhaustion in hostile tumour microenvironments, and loss of target antigen expression. Nanomaterials may uniquely overcome these barriers through rational design. IL-2-Fc fusion-protein-modified liposomes delivered to the surface of >95% of adoptively transferred T cells, inducing enhanced T-cell proliferation in tumour-bearing mice. - IL-15 superagonist nanogel backpacked onto.
Cancer immunotherapy has shown efficacy but is limited by serious adverse effects, nonspecific inflammation, and challenges in spatiotemporal control of immune responses. Nanomedicine and functionalized nanosystems offer programmable pharmacokinetics, co-delivery of immunomodulators, and targeted delivery, potentially improving immunotherapy outcomes. Antigen-capturing NPs (AC-NPs) plus αPD-1 improved cure rate by 20% in B16F10 melanoma, expanded CD8⁺ cytotoxic T cells, and increased CD4⁺/Treg and CD8⁺/Treg ratios. - Cationic lipid-assisted PEG-b-PLGA NPs (CLANs).
Est-Witte Se, Livingston Nk, Omotoso Mo, Green Jj, Schneck Jp.
T cell therapies (TIL, TCR, CAR T) show clinical efficacy but are limited by high cost, lengthy ex vivo manufacturing, patient variability, and poor persistence. Nanoparticles offer a modular, universal platform to improve T cell therapy at every stage—from antigen presentation and T cell activation to T cell maintenance—while reducing cost and broadening patient accessibility. Nano-aAPC E+E expanded Kb-TRP2 cognate cells from ~0.03% to 17.6% by day 7; nano-aAPCs expanded MART-1-specific CD8⁺ T cells more effectively than autologous DCs and CD3/CD28 Dynabeads, with higher stem cell memory.
Raza F, Zafar H, Zhang S, Kamal Z, Su J, Yuan W-E, Qiu M.
Cancer immunotherapy is limited by the immunosuppressive tumor microenvironment, patient heterogeneity, poor delivery of immunotherapeutics, and systemic immunotoxicity. Cell membrane-derived biomimetic nanoparticles may improve delivery and biodistribution, enhance targeting and immune stimulation, and overcome barriers faced by conventional nanomedicine. RBCM-coated nanoparticles improved half-life by up to 50% versus PEGylated nanoparticles and were detected in blood circulation after 72 h. - A size-reducible RBCM biomimetic system combined with.
Synthetic nanoparticles face physiological barriers, RES clearance, and unintended biological interactions despite PEGylation and ligand grafting. Biological vectors—cell membranes, extracellular vesicles (EVs), and viruses—offer biocompatibility, biodegradability, immune evasion, and natural targeting. This review summarizes BNPs integrating biological vectors with functional agents for targeted delivery in imaging and therapy. RBCM-coated PLGA nanoparticles improved half-life by ~50% vs PEGylated nanoparticles and were detected in circulation after 72 h. - NM-NP-CFZ (neutrophil membrane-coated carfilzomib PLGA NPs) reduced lung metastasis by.
Tumor microenvironment (TME) modulation is a promising strategy in cancer immunotherapy, but conventional immunotherapeutic agents suffer from limited drug retention in the TME, severe adverse events, and low response rates. Nanoparticles can prolong retention, enable targeted delivery to TME components, and convert the immunosuppressive TME into an immunosupportive state, potentially improving therapeutic efficacy while reducing toxicity. DC targeting: CD40-targeted PLGA nanoparticles achieved highest binding/uptake and maximum IL-12 production in vitro; however, T cell proliferation was driven mainly by TLR ligands rather than targeting ligand. -.
Cancer immunotherapy can produce durable clinical responses, but systemic delivery of immunostimulatory agents is limited by short half-lives, off-target toxicities (e.g., cytokine release syndrome), low response rates (10–30%), and poor efficacy in solid tumors. Polymeric micelles offer a biocompatible, modifiable, core–shell delivery platform that can improve bioavailability, enable tumor accumulation via the EPR effect, and reduce systemic. IL-2 micelles: Enhanced DC vaccine efficacy and increased antigen-specific CTL accumulation at tumor sites. - PMet-P(cdmPEG2K) micelles: Co-delivery of DOX and pIL-12 was more effective at inhibiting tumor growth than.
Polymeric nanoparticles are widely used for cancer theranostics because of their biocompatibility, biodegradability, and structural versatility, but conventional delivery still faces poor target specificity, uncontrolled release, and systemic toxicity. Stimuli-responsive polymeric nanoplatforms are proposed to exploit tumor microenvironment (TME) and external triggers to enable precise, on-demand drug/gene release at tumor sites. Representative findings highlighted in the review: - TME gradients: tumor extracellular pH is approximately 5.7–6.9 versus blood pH 7.4; intracellular GSH is 2–10 mM versus extracellular 2–10 µM; tumor ROS is about.
Melanoma is a poorly immunogenic and highly aggressive skin cancer with limited long-term survival for advanced disease. Dendritic cell (DC)-based vaccines are promising immunotherapies, but their efficacy relies on critical factors including DC maturation state and efficient antigen delivery. Nanoparticulate delivery systems can enhance antigen delivery to ex vivo-generated DCs, mediate DC maturation (adjuvanticity), and promote cytoplasmic antigen presentation through MHC class I—potentially leading to potent antigen-specific immune responses. This review addresses the need to consolidate and evaluate the role of different nanoparticulate delivery systems in ex vivo-generated DC-based vaccines against melanoma. --- - Fusogenic liposomes (FLs): TCL/FLs-pulsed DCs significantly inhibited tumor growth until 17 days post-inoculation; superior to TCL/CLs-pulsed DCs. - Cationic liposomes (Srinivas et al.): Lipid 5 (shikimoyl headgroup) indu
Kelly R. Rhodes, Randall A. Meyer, Justin Wang, Stephany Y. Tzeng, Jordan J. Green
Regulatory T cell (Treg)-based therapeutics show promise for treating autoimmune diseases and preventing transplant rejection, but adoptive Treg transfer is expensive, complex, and difficult to implement. "Off-the-shelf" non-cellular alternatives that can induce endogenous Tregs in vivo are needed. Existing artificial antigen presenting cells (aAPCs) are typically used for ex vivo T cell expansion and have limited application for immune. ### Protein Conjugation & aAPC Characterization | Parameter | PLGA aAPC | PLGA/PBAE aAPC | Significance | |---------------|---------------|--------------------|------------------| | Anti-CD3 conjugation (1× dose) |.
Elana Ben-Akiva, Randall A. Meyer, Hongzhe Yu, Jonathan T. Smith, Drew M. Pardoll, Jordan J. Green
Previous red blood cell (RBC) membrane-coated nanoparticles have all been spherical, missing the physical shape component of biomimicry. Particle shape is a critical design parameter affecting biodistribution, macrophage evasion, and targeted interactions. A platform combining physical biomimicry (anisotropic shape) with chemical biomimicry (RBC membrane coating) could improve circulation time and detoxification efficacy. Macrophage uptake: RBC membrane coating reduced uptake by 30–50%; anisotropic shape reduced uptake by 30–40%; combined coating + anisotropy reduced uptake by 50–70% versus spherical uncoated particles at 4 h. - Blood.
DNA vaccines require high doses because naked DNA is poorly delivered to antigen-presenting cells (APCs), and conventional PLGA microsphere encapsulation by W/O/W emulsion can damage DNA, lower supercoiled DNA content, and give low encapsulation efficiency. A controlled-release system is needed that protects DNA during formulation and enhances immunogenicity at lower doses. Polyplex characterization: PEG-g-PEI/DNA polyplexes at N/P = 20 had a size of 74.1 ± 21.2 nm and zeta potential of 11.47 ± 0.78 mV; transfection peaked at N/P ≥ 20, and cell viability was >90% at N/P ≤ 20. - NIM.
Xueguang Lu, Lei Miao, Wenting Gao, Ziqi Chen, Kevin J. Mchugh, Yehui Sun, Zachary Tochka, Stephanie Tomasic, Kaitlyn Sadtler, Alain Hyacinthe, Yuxuan Huang, Tyler Graf, Quanyin Hu, Morteza Sarmadi, Robert Langer, Daniel G. Anderson, Ana Jaklenec
STING agonists require frequent intratumoral injections over months to achieve efficacy, leading to poor patient adherence, repeated disruption of the tumor microenvironment, increased metastasis risk, and limited applicability to hard-to-reach tumors. A single-injection delivery system that mimics multiple dosing would improve adherence, reduce metastasis risk, and expand clinical utility. Pulsatile release: Microparticles released cargo in pulses at approximately 1, 4, 8, 11, 15, 18, and 97 days in vitro with no detectable leakage before release. In vivo release times for PLGA-1, PLGA-2, and PLGA-3 were.
Serkan Yaman, Harish Ramachandramoorthy, Gizem Oter, Daria Zhukova, Tam Nguyen, Manoj K. Sabnani, Jon A. Weidanz, Kytai T. Nguyen
Melanoma is an aggressive skin cancer with limited treatment efficacy due to non-specific drug targeting, severe side effects, and multidrug resistance. Current cell-based immunotherapies are costly, complex, and carry long-term autoimmune risks. There is a need for a targeted, biocompatible drug delivery system that selectively recognizes melanoma cells and provides sustained drug release. Physicochemical properties: T-MNPs (1:2) were 193 ± 56 nm, PDI 0.265, zeta −36 mV; stable in saline for 48 h. Drug loading 61%; sustained trametinib release over 28 days, slowest at highest membrane ratio (1:2). - TCR.
