Papers, explained in our own words

1. Cationic nanoparticles enhance T cell tumor infiltration and antitumor immune responses to a melanoma vaccine

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 |.

2. Imidazole-based Synthetic Lipidoids for In Vivo mRNA Delivery into Primary T Lymphocytes

Xuewei Zhao, Jinjin Chen, Min Qiu, Yamin Li, Zachary Glass, Qiaobing Xu

In vivo engineering of T lymphocytes is limited by poor transfection efficiency and reliance on ex vivo electroporation. A non-viral mRNA delivery platform that can target primary T cells in vivo is needed for CAR T-cell therapy, vaccines, and immunotherapy. Rough screening identified imidazole head 93 with O17O, O17S, and O17Se tails as effective for mRNA delivery to primary T cells; Lipofectamine 2000 was poor. - Detailed screening identified 93-O17S and 9322-O17S as top.

3. Nanoparticles for dendritic cell-based immunotherapy

Tran Th, Tran Ttp, Nguyen Ht, Phung Cd, Jeong J-H, Stenzel Mh, Jin Sg, Yong Cs, Truong Dh, Kim Jo.

Dendritic cell (DC)-based cancer immunotherapy is promising but limited by poor antigen immunogenicity, weak stability, and short in vivo half-life. Nanotechnology can protect antigens and adjuvants from premature degradation, enhance delivery to DCs, and improve therapeutic T cell responses. This review summarizes recent advances in nanoparticle-based systems for DC-targeted cancer immunotherapy. PLGA-conjugated or encapsulated Hp91 peptide activated DCs 5-fold (encapsulated) and 20-fold (surface-conjugated) more potently than free peptide. - Co-delivery of TRP2 and 7-acyl lipid A in PLGA NPs significantly.

4. pH-sensitive polymer-modified liposome based immunity-inducing system Effects of inclusion of cationic lipid and CpG-DNA

Yoshizaki Y, Yuba E, Sakaguchi N, Koiwai K, Harada A, Kono K

Efficient cancer vaccine carriers need both antigen delivery to dendritic cells (DCs) and DC activation. Previous pH-sensitive polymer-modified liposomes delivered antigen to DC cytosol but had limited adjuvant potency, and combining cationic lipid TRX with MPLA reduced antitumor effects, suggesting a need for alternative adjuvant combinations and controlled CpG-DNA delivery to endosomal TLR9. CpG-DNA binding: Pre-mix TRX+ bound >80% of CpG-DNA in feed; Pre-mix TRX− bound <13%. After 24 h, only 3.7 ± 1.3% of CpG-DNA was detected in supernatant, indicating >96% stable binding. - OVA loading: TRX inclusion.

5. Enhanced antitumor immunity by targeting dendritic cells with tumor cell lysate-loaded chitosan nanoparticles vaccine

Shi Gn, Zhang Cn, Xu R, Niu Jf, Song Hj, Zhang Xy, Wang Ww, Wang Ym, Li C, Wei Xq, Kong Dl

Whole tumor cell lysates (TCL) are a broad source of tumor antigens for cancer vaccines, but soluble TCL is unstable, poorly taken up by dendritic cells (DCs), and inefficient at inducing cytotoxic T lymphocyte (CTL) responses. A delivery system was needed to protect TCL antigens, target DCs, and enhance antigen presentation and antitumor immunity. Nanoparticle characterization: Man-CTS-TCL NPs were ~120 nm, spherical, with a zeta potential of ~ −12 mV. Protein release was elevated at pH 5.0 compared with pH 7.4. - DC uptake/maturation: Man-CTS-TCL NPs increased.

6. Human immune cell targeting of protein nanoparticles – caveospheres

Joshua J. Glass, Daniel Yuen, James Rae, Angus P. R. Johnston, Robert G. Parton, Stephen J. Kent, Robert De Rose

Investigations of nanoparticle targeting to immune cells are conventionally restricted to monocultured cell line models that lack the complexity of primary human blood cell populations, including non-specific association with, and competition from, diverse cell types. A more physiologically relevant system using mixed primary human blood cells is needed to evaluate nanoparticle targeting, particularly for therapeutically relevant non-phagocytic. ### Nanoparticle Characterization | Parameter | Untargeted | αCD4 | αCD20 | |---------------|---------------|----------|-----------| | EM diameter (nm) | 42.7 ± 8.3 | 41.3 ± 8.3 | 45.3 ± 6.8 | | DLS hydrodynamic size.

7. Type I Interferons Interfere with the Capacity of mRNA Lipoplex Vaccines to Elicit Cytolytic T Cell Responses

Ans De Beuckelaer, Charlotte Pollard, Sandra Van Lint, Kenny Roose, Lien Van Hoecke, Thomas Naessens, Vimal Kumar Udhayakumar, Muriel Smet, Niek Sanders, Stefan Lienenklaus, Xavier Saelens, Siegfried Weiss, Guido Vanham, Johan Grooten & Stefaan De Koker

mRNA vaccines are promising for inducing cytolytic CD8⁺ T cell responses, and lipoplex carriers improve mRNA delivery to dendritic cells. However, the innate factors that regulate T cell induction by mRNA lipoplex vaccines remain unresolved. In particular, type I interferons (IFNs) are induced by mRNA but can either promote or inhibit T cell immunity depending on context. mRNA lipoplexes induced potent type I IFN responses after subcutaneous, intradermal, and intranodal injection. Naked mRNA also induced IFN-β, whereas liposomes alone did not, indicating IFN induction is inherent to mRNA.

8. Antigen-Loaded Upconversion Nanoparticles for Dendritic Cell Stimulation, Tracking, and Vaccination in Dendritic Cell-Based Immunotherapy

Jian Xiang, Ligeng Xu, Hua Gong, Wenwen Zhu, Chao Wang, Jun Xu, Liangzhu Feng, Liang Cheng, Rui Peng, Zhuang Liu

Dendritic cell (DC)-based immunotherapy requires efficient antigen delivery into DCs, DC maturation, and migration to draining lymph nodes, but real-time tracking of DC migration remains challenging with traditional methods (e.g., FITC painting). While upconversion nanoparticles (UCNPs) offer advantages for sensitive imaging with minimal autofluorescence, their application for simultaneous antigen delivery, DC stimulation, tracking, and. ### Nanoparticle Characterization & OVA Loading | Parameter | UCNP | UPP | UPP@OVA | |---------------|----------|---------|-------------| | Zeta potential | +12.5 mV | +40.1 mV | +29.4 mV | | Hydrodynamic size | ~170 nm.

9. Targeting nanoparticles to CD40, DEC-205 or CD11c molecules on dendritic cells for efficient CD8+ T cell response: A comparative study

Luis J. Cruz, Rodney A. Rosalia, Jan Willem Kleinovink, Felix Rueda, Clemens W.G.M. Löwik, Ferry Ossendorp

Dendritic cell (DC)-based therapies have shown clinical benefits but are hampered by labor-intensive, GMP-regulated vaccine preparations requiring multiple steps and donor variability. In vivo targeting of antigens to DC surface receptors using nanoparticle delivery systems could circumvent these drawbacks. However, it is not fully clear which cell surface molecule or receptor expressed by DC should be targeted for optimal T cell activation. A. ### Nanoparticle Characterization | Parameter | Non-Targeted | αCD40 | αDEC-205 | αCD11c | |---------------|------------------|-----------|--------------|------------| | Size (nm) | 186.6 ± 9.0 | 200.7 ± 12.5 | 198.2 ±.

10. A Carbon Nanotube–Polymer Composite for T-Cell Therapy

Tarek R. Fadel, Fiona A. Sharp, Nalini Vudattu, Ragy Ragheb, Justin Garyu, Dongin Kim, Enping Hong, Nan Li, Gary L. Haller, Lisa D. Pfefferle, Sune Justesen, Kevan C. Herold, Tarek M. Fahmy

Adoptive cell transfer of tumor-specific T cells is a promising cancer immunotherapy, but efficient and economical ex vivo expansion of T cells remains a bottleneck. Artificial antigen-presenting cells (aAPCs) with high surface area and modular design could overcome cost and scalability limits of dendritic cell–based expansion. Murine T-cell expansion: CNPs expanded OT-1 CD8⁺ T cells ~200-fold after 2 weeks—more than 2× DYNA-EXO and more than 4× TET-EXO. - Cytokine efficiency: Expansion comparable to clinical standards using 1,000-fold less.

11. PLGA-nanoparticle mediated delivery of anti-OX40 monoclonal antibody enhances anti-tumor cytotoxic T cell responses

Mingshui Chen, Haichao Ouyang, Shangyong Zhou, Jieyu Li, Yunbin Ye

Agonistic anti-OX40 monoclonal antibody (mAb) can enhance anti-tumor immunity in preclinical models, but as monotherapy it showed only marginal activity and no objective clinical responses in a phase I trial. A delivery system that improves T cell access, multivalent OX40 engagement, and sustained release of anti-OX40 mAb could enhance cytotoxic T lymphocyte (CTL) responses for cancer immunotherapy. Nanoparticle properties: Size 86.0 ± 14.1 nm; zeta potential −12.8 ± 1.5 mV; encapsulation efficiency 65.8 ± 5.6%; loading ~25% (248 ± 16.3 µg mAb/mg polymer); sustained release ~55% over 20 days with no initial burst.

12. Lipid-based carriers of microRNAs and intercellular communication

Vickers Kc, Remaley At

Extracellular miRNAs are unusually stable in plasma and their circulating levels change with disease, making them promising biomarkers. They are associated with lipid-based carriers—exosomes, microvesicles, apoptotic bodies, and lipoproteins—as well as lipid-free proteins. Whether these carriers mediate functional miRNA transfer between cells and act as a form of intercellular communication was the central gap addressed. Over 1,500 human miRNAs have been curated; each cell type typically contains ~150–300 miRNAs. - HDL was shown to contain miRNAs and deliver them to Huh7 hepatocellular carcinoma cells and SR-BI–overexpressing BHK cells.

13. Polymer Nanoparticles Containing Tumor Lysates as Antigen Delivery Vehicles for Dendritic Cell–Based Antitumor Immunotherapy

Shashi Prasad, Virginia Cody, Jennifer K. Saucier-Sawyer, W. Mark Saltzman, Clarence T. Sasaki, Richard L. Edelson, Martin A. Birchall, Douglas J. Hanlon

Efficient antigen delivery remains a major challenge for dendritic cell (DC)-based immunotherapy of solid-organ malignancies. Soluble tumor lysates suffer from instability, poor DC internalization, and inefficient cross-presentation to cytotoxic T lymphocytes. PLGA nanoparticles may protect antigens, improve loading, prolong release, and enhance MHC-peptide presentation. Encapsulation: Increased with lysate concentration; Pearson correlation 0.92 for 45-kDa PLGA and 0.95 for 80-kDa PLGA. Lyophilized lysate improved encapsulation and release. - Release: Biphasic release over 7 days;.

14. Activation of Antigen-Specific T Cell-Responses by Mannan-Decorated PLGA Nanoparticles

Samar Hamdy, Azita Haddadi, Anooshirvan Shayeqanpour, John Samuel, Afsaneh Lavasanifar

Mannosylation of vaccine formulations is a promising strategy to target antigens to the mannose receptor (MR) on dendritic cells (DCs), potentially improving antigen uptake, processing, and presentation. While PLGA nanoparticles (NPs) are established vaccine delivery vehicles, the effect of chemical conjugation of mannan (MN) to antigen-loaded PLGA-NPs on antigen-specific T-cell responses was not fully characterized. This study addresses whether. DC Uptake: - OVA/FITC-Mannan-NPs: 64% FITC⁺ cells vs. 58% for OVA/FITC-NPs; MFI 305 vs. 295. - Double-positive FITC⁺/CD11c⁺ cells: 55.1% (MN-decorated) vs. 50.4% (non-decorated). In Vitro T-Cell Activation: -.

15. Targeted PLGA nano- but not microparticles specifically deliver antigen to human dendritic cells via DC-SIGN in vitro

Luis J. Cruz, Paul J. Tacken, Remco Fokkink, Ben Joosten, Martien Cohen Stuart, Fernando Albericio, Ruurd Torensma, Carl G. Figdor

Antibody-mediated targeting of vaccine components to dendritic cells (DCs) enhances vaccine efficacy, but linking multiple antigens and immune modulators to a single antibody is limited. Slow-release PLGA particles conjugated to DC-specific antibodies could overcome this by delivering large antigen payloads and enabling co-encapsulation of adjuvants. However, it was unknown whether nano- or micrometer-sized PLGA particles are better suited for. Particle characterization: MPs ~2 µm, NPs ~200 nm; PEG-lipid coating reduced zeta potential; antigen encapsulation 78–91%; antibody conjugation ~20–30 µg/mg PLGA. - Antigen degradation kinetics: Encapsulated antigen.

16. Small Molecule End Group of Linear Polymer Determines Cell-Type Gene Delivery Efficacy

Joel Sunshine, Jordan J. Green, Kerry P. Mahon, Fan Yang, Ahmed A. Eltoukhy, David N. Nguyen, Robert Langer, Daniel G. Anderson

Viral vectors are efficient but face safety, manufacturing, and cargo-capacity limitations. Cationic polymers such as poly(β-amino ester)s (PBAEs) are promising non-viral alternatives, but their gene delivery efficacy varies across cell types. The study asked whether small-molecule end groups on a linear PBAE could determine cell-type–specific gene delivery efficacy. End-group effect: Transfection ranged from <1% to >90% positive cells depending on end group and cell type. - Lead polymers per cell type: COS-7: C32-206; HeLa: C32-213; HepG2: C32-210; HUVEC: C32-117; DC2.4: C32-254;.

17. Co-delivery of cancer-associated antigen and Toll-like receptor 4 ligand in PLGA nanoparticles induces potent CD8⁺ T cell-mediated anti-tumor immunity

S. Hamdy, O. Molavi, Z. Ma, A. Haddadi, A. Alshamsan, Z. Gobti, S. Elhasi, J. Samuel, A. Lavasanifar

Most PLGA-based cancer vaccine studies used foreign model antigens such as ovalbumin (OVA), which are not subject to central/peripheral tolerance and can overestimate therapeutic efficacy. There is a need to evaluate PLGA vaccines against a realistic, clinically relevant self/tumor antigen (TRP2) and to overcome self-tolerance and the immunosuppressive tumor microenvironment. Co-delivery of a TLR4 ligand (7-acyl lipid A) with a tumor antigen in. Nanoparticle Characterization: - Size 350–410 nm, PDI < 0.2. - TRP2 EE 5.2 ± 0.6%; loading 0.94 ± 0.11 µg/mg. - 7-acyl lipid A EE 67.3 ± 6.9%; loading 1.79 ± 0.18 µg/mg. Normal Mice Vaccination (ELISPOT): - Empty-NP: no.

18. Polymer Nanoparticles for Immunotherapy from Encapsulated Tumor-Associated Antigens and Whole Tumor Cells

C. M. Solbrig, J. K. Saucier-Sawyer, V. Cody, W. M. Saltzman, D. J. Hanlon

Current antitumor vaccines are limited by the small number of defined tumor-associated antigens (TAAs) for most solid tumors and by poor delivery of soluble antigen to dendritic cells (DCs). Autologous whole-tumor lysates contain the full antigenic repertoire, but soluble lysates are unstable and poorly internalized. Biodegradable PLGA nanoparticles may protect antigens, improve DC uptake, and enhance cross-presentation to cytotoxic T cells. Encapsulation: Efficiency increased with PLGA molecular weight and decreased with initial protein loading. For OVA at 50 mg/mL loading: 15K = 27%, 45K = 22%, 80K = 55%, 105K = 99%. At 100 mg/mL loading, encapsulation.

19. Controlled release of PEI/DNA complexes from mannose-bearing chitosan microspheres as a potent delivery system to enhance immune response to HBV DNA vaccine

Xianfeng Zhou, Bin Liu, Xianghui Yu, Xiao Zha, Xizhen Zhang, Yu Chen, Xueyun Wang, Yinghua Jin, Yongge Wu, Yue Chen, Yaming Shan, Yan Chen, Junqiu Liu, Wei Kong, Jiacong Shen

DNA vaccines can induce antibody and CTL responses, but clinical translation is limited by weak potency and the need for high or repeated doses. The study addresses this by targeting DNA to antigen-presenting cells (APCs) and improving endosomal/lysosomal release, using mannose-bearing chitosan microspheres loaded with PEI/DNA complexes for an HBV DNA vaccine. Microsphere characterization: m-chitosan microspheres were 326.3 ± 31.9 nm, with 89 ± 2.6% DNA encapsulation efficiency and zeta potential 10.19 ± 3.23 mV. u-chitosan microspheres were 415.2 ± 44.2 nm, 94 ± 5.4%.

20. Prophylactic anti-tumor effects in a B cell lymphoma model with DNA vaccines delivered on polyethylenimine (PEI) functionalized PLGA microparticles

DNA vaccines are limited by inefficient delivery to antigen-presenting cells (APCs) and lack of adjuvant effect, especially for weakly immunogenic self/tumor antigens. The study addresses this by using cationic PEI-functionalized PLGA microparticles to enhance APC activation and protective anti-tumor immunity against B cell lymphoma. Particle properties: Zeta potentials: unmodified PLGA −10.4 mV; branched PEI70k +37.69 mV; branched PEI25k +37.74 mV; linear PEI25k +44.9 mV. Most particles were <10 µm. - DNA release: Linear PEI particles released ~60%.

21. PLGA microspheres for improved antigen delivery to dendritic cells as cellular vaccines

Ying Waeckerle-Men And Marcus Groettrup

Dendritic cell (DC)-based vaccines are limited by the short persistence of MHC class I/peptide complexes on the DC surface—often only a few hours—when soluble peptides are loaded exogenously. This short presentation limits CTL activation and vaccine efficacy. The authors investigated biodegradable PLGA microspheres (PLGA-MS) as an antigen delivery system to human monocyte-derived DC (hMoDC), aiming to prolong antigen presentation on both MHC. Uptake: Immature hMoDC took up 10–30 PLGA-MS per cell within 1–4 h; 61% of cells were FITC-MS positive by flow cytometry. - Direct vaccination: A single injection of 20 µg TT in PLGA-MS yielded antibody titers.

22. Caveolae and Caveolin in Immune Cells: Distribution and Functions

James Harris, Dirk Werling, Jayne C. Hope, Geraldine Taylor, Chris J. Howard

Caveolae and caveolin are cholesterol-rich membrane microdomains involved in endocytosis, cholesterol regulation, and signal transduction, but their presence and function in immune cells have been contentious. This review addresses the need to clarify the distribution and roles of caveolae/caveolin in mammalian immune cells, especially given emerging evidence that they mediate pathogen internalization by antigen-presenting cells and participate in immune-cell signaling. --- 1. Distribution is contentious and context-dependent: Caveolae/caveolin are commonly found in myeloid cells (macrophages, mast cells, dendritic cells, neutrophils) but not consistently in lymphoid cells. More recent evidence suggests they may be present in all immune cell types, with expression/distribution dependent on activation and/or maturation state. 2. Species and cell-type differences in caveolin localization: Human CD26+ and CD21+ peripheral blood lymphocytes