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.
siRNA therapeutics are limited by poor cellular uptake, serum nuclease degradation, and inefficient endosomal/lysosomal escape. Chitosan is biocompatible and biodegradable but has low transfection efficiency, largely due to poor buffering capacity and weak endosomal escape. Histidine grafting was explored to add imidazole groups (pKa ~6) that enhance proton-sponge buffering and siRNA delivery. Synthesis: FT-IR showed amide C=O at 1640 cm⁻¹ and N–H bending shift from 1590 to 1522 cm⁻¹; histidine O–H at 3016 cm⁻¹ disappeared. XRD showed loss of histidine crystal peaks at 18.8° and 24.3°, and HGCS polymers were.
Self-healing polymers can repair damage and recover functionality, potentially extending the lifetime and safety of biomedical devices. Although self-healing hydrogels have been reviewed previously, papers focused specifically on their use in tissue engineering are scarce. This review summarizes fabrication methods, polymers, biomedical examples, and recent progress in self-healing polymers for tissue engineering. Acylhydrazone-crosslinked nanocomposite hydrogel: self-healing efficiency 97.5%; nearly 100% cell viability. - P(BAL-co-DMSA) hydrogel: self-healing within ~5 s in air and underwater; stretchability ~4500%; complete.
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
Hashemi V, Farhadi S, Ghasemi Chaleshtari M, Et Al.
Dendritic cell (DC)-based cancer immunotherapy has shown impressive outcomes, including the first FDA-approved anti-cancer vaccine, but clinical application faces challenges such as limited durable responses, antigen selection issues, and immunosuppressive tumor microenvironments. Nanoparticles (NPs) are promising for antigen/adjuvant delivery to DCs and can enhance T cell-stimulating effects while minimizing toxicity. This review surveys cancer. PLGA NPs conjugated/loaded with Hp91 increased DC activation via CD40/CD80 upregulation and IL-6 secretion; in HER2-specific CD8+ T cells, this arrested tumor growth and increased survival. - PLGA NPs loaded with.
Conventional systemic drug administration suffers from low site-specific bioavailability, unfavorable biodistribution, poor target accumulation, and adverse side effects. There is a need for carrier-based systems that enable localized and targeted delivery, improve therapeutic efficacy, and reduce toxicity. Dual-targeted DOX/SPION SLNs enhanced accumulation at colon tumor sites and effectively inhibited orthotopic colon tumor in mice after oral administration. - Liposomal DOX plus MRP1/BCL2 siRNA by inhalation showed high.
Thomas, T. J.; Tajmir-Riahi, H.-A.; Pillai, C. K. S
Gene therapy requires efficient delivery of genetic material, but viral vectors carry risks of immunogenicity, toxicity, and cancer formation. Cationic polymers such as polyethyleneimine (PEI) can condense DNA and facilitate delivery, but their lack of biodegradation causes significant toxicity due to polymer accumulation in tissues. This review addresses the need for biodegradable polymeric gene delivery vehicles developed over the past decade. PEI: ~20% of nitrogen protonated at physiological pH; 22 kDa linear PEI showed more facile nuclear delivery than branched PEI. Non-degradable PEI causes severe cytotoxicity. - Biodegradable PEI derivatives: Reducible.
Juan Chen, Xiaobing Yang, Liuqing Huang, Huixian Lai, Chuanhai Gan, Xuetao Luo
Lung cancer has the highest mortality among cancers, and single-agent chemotherapy is often unsuccessful due to drug resistance, insufficient intracellular uptake, nonspecific targeting, and severe systemic toxicity. Combination chemotherapy can suppress drug resistance and achieve synergistic anticancer efficacy, but there is a need for targeted nanocarrier systems that can co-deliver multiple chemotherapeutic agents while providing active. ### Nanoparticle Characterization | Parameter | Result | |---------------|------------| | Hydrodynamic diameter (DLS) | 176 nm | | TEM core diameter | ~80 nm | | Polydispersity index (PDI) | 0.109 ± 0.034 | | Zeta.
Biodegradable polymeric nanoparticles have great potential to improve cancer therapy by enabling targeted delivery, triggered release, and reduced off-target toxicity. This review addresses how such nanocarriers can be engineered to overcome systemic, organ-level, and cellular barriers and to target cancer cells, tumor vasculature, and immune cells for anticancer therapy. PBAE nanoparticles delivered DNA encoding CAR to T cells in vivo; reprogrammed T cells expressed CAR for weeks, causing tumor regression and prolonged survival in a mouse leukemia model. - PLA nanoparticles delivering.
Shahed Behzadi, Vahid Serpooshan, Wei Tao, Majd A. Hamaly, Mahmoud Y. Alkawareek, Erik C. Dreaden, Dennis Brown, Alaaldin M. Alkilany, Omid C. Farokhzad, Morteza Mahmoudi
Nanoparticles (NPs) are increasingly used in consumer goods, electronics, and pharmaceuticals, but their beneficial and/or deleterious effects ultimately arise from interactions at the cellular and subcellular level. While many NPs require safe entry into cells for therapeutic efficacy, efficient and controlled entry/trafficking remains a major challenge. A comprehensive understanding of NP cellular uptake and trafficking mechanisms is critical for designing efficient and safe nanomedicines. --- - Size: ~50 nm is the optimum size for highest cellular uptake in certain cells; larger particles (1000–2000 nm) show maximal phagocytic uptake; smaller NPs (2.1 nm) can enter the nucleus/nucleoli, while 4.4 nm NPs show reduced penetration. - Shape: Spherical NPs undergo higher cellular uptake than rod-shaped NPs; lower aspect ratio rods are taken up faster than higher aspect ratio rods; rod and disc NPs are taken up twice as quickly as spheres
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.
Matthias Van Woensel, Nathalie Wauthoz, Rémi Rosière, Véronique Mathieu, Róbert Kiss, Florence Lefranc, Brecht Steelant, Ellen Dilissen, Stefaan W. Van Gool, Thomas Mathivet, Holger Gerhardt, Karim Amighi, Steven De Vleeschouwer
Galectin-1 (Gal-1) is overexpressed in glioblastoma multiforme (GBM), promotes tumor progression, angiogenesis, chemoresistance, and immune suppression. A non-invasive delivery strategy is needed to reach CNS tumors with siRNA while limiting systemic effects. The intranasal route was explored as an underexplored pathway for delivering siRNA-loaded chitosan nanoparticles to GBM. Nanoparticle characteristics: Optimal formulation had Z-average 141 ± 5 nm, PDI 0.3, zeta potential +32 mV, siRNA payload 24 µg/mL, and encapsulation efficiency 81 ± 3%. Freeze-dried particles stored at 4°C remained.
Niu Z, Conejos-Sánchez I, Griffin Bt, O’driscoll Cm, Alonso Mj
Peptide and protein therapeutics are highly potent but mostly require parenteral administration because they are degraded in the gastrointestinal tract, poorly permeate the intestinal epithelium, and have low oral bioavailability. Lipid-based nanocarriers are a promising strategy to enable oral peptide delivery by protecting cargo, enhancing permeability, reducing proteolysis, and promoting lymphatic transport. Protein/peptide therapeutic market projected at $180 billion by 2018. - SLNs achieved insulin AE up to 97.8% and DL up to 18.92%; sCT AE ~90%; leuprolide AE ~75%. - Micro/nanoemulsions achieved >80% entrapment for.
Li, Y.; Maciel, D.; Rodrigues, J.; Shi, X.; Tomás, H
Despite extensive research, therapeutic delivery still faces major barriers: poor plasma stability, rapid clearance by the reticuloendothelial system (RES), and intracellular obstacles such as endosomal entrapment and lysosomal degradation. Biodegradable polymer nanogels (NGs) — physically or chemically cross-linked, water-swollen, submicrometer hydrophilic polymer networks — are promising because they can encapsulate or conjugate drugs/nucleic. Chitosan/alginate NGs improved gene transfection in 293T cells 4-fold compared with CTS NGs without alginate. - Redox-sensitive HA NGs protected siRNA; 94% remained entrapped after 110 min without GSH, while at 10 mM.
Viral vectors are efficient but carry risks of immunogenicity, inflammatory reactions, recombination, limited DNA cargo capacity, and manufacturing difficulties. Non-viral polymeric vectors are safer and easier to produce, but their transfection efficiency remains much lower than viral vectors because of multiple extracellular and intracellular barriers. This review summarizes these barriers and recent strategies to overcome them using polymeric. Optimal size: Non-targeting cationic vector–DNA complexes are most effective at 70–90 nm; microparticles of 1–10 µm are preferentially taken up by phagocytic antigen-presenting cells. - PLL: Low buffering capacity (pH.
Héloïse Ragelle, Raphaël Riva, Gaëlle Vandermeulen, Broes Naeye, Vincent Pourcelle, Cécile S. Le Duff, Cécile D’haese, Bernard Nysten, Kevin Braeckmans, Stefaan C. De Smedt, Christine Jérôme, Véronique Préat
Naked siRNA is unstable and inefficient, and chitosan-based carriers are limited by poor solubility at physiological pH and weak endosomal disruption. The study aimed to optimize chitosan nanoparticle formulations for intravenous siRNA delivery that achieve high gene silencing without cytotoxicity and remain stable in biological fluids including blood. Basic chitosan/TPP nanoparticles showed poor transfection regardless of chitosan type. - PEI-containing PEGylated formulations achieved high silencing: C_PEG/PEI l = 71%, C_PEG/PEI h = 62%, C3/C_PEG/PEI = 66% luciferase.
Kyung Hee Noh, Yeong Min Park, Hyuk Soon Kim, Tae Heung Kang, Kwon‐ho Song, Young‐ho Lee, Yeongseon Byeon, Hat Nim Jeon, In Duk Jung, Byung Cheol Shin, Kyung‐mi Lee, Seung‐yong Seong, Hee Dong Han, Tae Woo Kim
Conventional adjuvants such as Complete Freund’s Adjuvant (CFA) and Incomplete Freund’s Adjuvant (IFA) are potent but toxic, limiting clinical use. A safer, biodegradable adjuvant system was needed to enhance antigen-specific humoral and cellular immunity without severe local or systemic side effects. Safety: CH-HG formed a local hydrogel after subcutaneous injection, caused no pus, discharge, or scab, and was largely degraded by 2 weeks. CH-HG-injected mice maintained body weight similar to controls, whereas CFA-.
Gan L, Wang J, Jiang M, Bartlett H, Ouyang D, Eperjesi F, Liu J, Gan Y
Topical ocular drug delivery is limited by tear turnover, corneal and conjunctival barriers, efflux transporters, and poor water solubility of many drug candidates. Lipid-based nanocarriers may improve ocular bioavailability, prolong preocular residence, enhance corneal penetration, and provide controlled release. Typically <5% of a topically applied drug penetrates the cornea and sclera to reach intraocular tissue. - Tear turnover is about 16% per minute during waking hours; reflex lachrymation can increase tear flow up to 300.
Chitosan is attractive for siRNA delivery because it is cationic, biocompatible, biodegradable, mucoadhesive, and permeation-enhancing. However, native chitosan suffers from low solubility at physiological pH, poor buffering capacity, instability in biological fluids, and insufficient endosomal escape, limiting gene-silencing efficiency. This review addresses these barriers and the strategies developed to overcome them. Chitosan molecular weight: High MW (114–170 kDa) yielded up to 65% GFP silencing; low MW (9–12 kDa) gave <5%. 25 kDa chitosan showed almost no silencing; 50 kDa gave 50% in OV-3 and 10% in HeLa. - N/P ratio: 50–150 was.
Viral vectors give high gene-transfer efficiency but carry risks of immunogenicity, oncogenic transformation, limited cargo capacity, and manufacturing difficulty. Nonviral nanocarriers are safer and cheaper alternatives, but they still suffer from low transfection efficiency because of extracellular and intracellular barriers. This review addresses the need to comparatively understand lipid, polymer, and inorganic material platforms and their design rules for efficient intracellular nucleic acid delivery. --- - Lipidoid library: >1,200 lipid-like materials screened; achieved siRNA silencing comparable to Lipofectamine 2000 in vitro and in mouse/rat liver in vivo. - Gold–PEI nanoparticles: transfection efficiency ~12-fold more potent than PEI alone in COS-7 cells; quaternary ammonium AuNPs ~8-fold more effective than PEI in 293T cells. - Chitosan/siRNA: knockdown up to 90% in a papillary thyroid carcinoma model. - Carbon nanotube–siRNA:
Fabienne Danhier, Eduardo Ansorena, Joana M. Silva, Regis Coco, Aude Le Breton, Véronique Préat
PLGA is one of the most successfully developed biodegradable polymers, with FDA and EMA approval for parenteral drug delivery, but a comprehensive overview linking its formulation methods, physicochemical pitfalls, targeting strategies, and applications across multiple diseases was needed. This review presents why PLGA has been chosen for nanoparticle-based drug delivery and how its properties can be exploited to target specific organs, tissues. Encapsulation efficiency and drug loading: EE varies widely from 6% (dexamethasone) to 90% (paclitaxel); mean EE around 60–70% for drugs such as estradiol or xanthones. However, drug loading is generally poor—around 1%.
Chemo-immunotherapy combinations are limited by systemic immunotoxicity from cancer drugs and rapid clearance of low-molecular-weight drugs after intratumoral injection. A local, biodegradable delivery system was needed to sustain drug/GMCSF exposure at the tumor site, reduce systemic toxicity, and promote tumor antigen cross-presentation and CD8+ T cell-mediated anti-tumor immunity. Tumor growth: CH containing cancer drug + GMCSF significantly reduced TC-1 tumor growth compared with CH–cancer drug alone, CH-GMCSF, or CH alone. CTX was the most potent drug in combination with GMCSF. Fig. 1 reported.
Han Hd, Mangala Ls, Lee Jw, Shahzad Mmk, Kim Hs, Shen D, Nam Ej, Mora Em, Stone Rl, Lu C, Lee Sj, Roh Jw, Nick Am, Lopez-Berestein G, Sood Ak
siRNA has therapeutic potential, but in vivo delivery is limited by rapid clearance, nuclease degradation, and nonspecific distribution. A tumor-targeted, biocompatible delivery system was needed to increase intratumoral siRNA accumulation, reduce off-target effects, and enable silencing of growth-promoting genes in ovarian cancer. Nanoparticle binding: In αvβ3-positive SKOV3ip1 cells, binding increased with RGD concentration; siRNA/RGD-CH-NP 5 showed highest binding, with 94.25% binding efficiency versus CH-NP. Little binding occurred in.
Parhamifar, L.; Larsen, A. K.; Hunter, A. C.; Andresen, T. L.; Moghimi, S. M
Efficient transfection with low toxicity is essential for nucleic acid therapeutics, but synthetic polycations such as polyethylenimine (PEI) are limited by cytotoxicity. This review critically assesses the safety and efficacy challenges of PEI-based polyplexes, identifies deficiencies in the field, and proposes avenues for designing safer polycationic vectors for clinical gene therapy and RNA interference delivery. Branched 25 kDa PEI is among the most efficient polycationic transfectants but also among the most cytotoxic. - PEI polyplexes damage plasma membranes, causing phosphatidylserine redistribution and LDH leakage without.
Nucleic acid therapeutics—plasmid DNA, antisense oligonucleotides, and RNAi molecules—have broad therapeutic potential but face major biological barriers, including nuclease degradation, poor membrane penetration, endosomal entrapment, nonspecific biodistribution, and immune activation. The review addresses how lipid- and polymer-based carriers can be designed to overcome these barriers and improve nucleic acid delivery. Pyridinium lipids with trans configuration showed higher transfection than cis counterparts; C16:1 unsaturated lipids outperformed C18:1 and C20:1; amide linkers generally gave higher transfection than ester linkers. -.
