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.
Annabelle Biscans, Socheata Ly, Nicholas Mchugh, David A. Cooper, Anastasia Khvorova
Lipid-conjugated siRNAs can reach extrahepatic tissues, but silencing efficacy remains lower than in liver largely because only ~1–2% of internalized siRNA escapes endosomes into the cytoplasm. Ionizable lipids enhance endosomal escape in lipid nanoparticles (LNPs), but direct covalent conjugation of an ionizable lipid to siRNA had not been investigated. DLin-MC3-DMA conjugation retained RISC activity in vitro: IC50 values were 322 pM (unconjugated), 365 pM (cholesterol), and 481 pM (DLin-MC3-DMA). - Endosomal escape was enhanced: DLin-MC3-DMA-siRNA increased Gal8+.
Mingyuan Li, Yuan Li, Shiqin Li, Lin Jia, Haomeng Wang, Meng Li, Jie Deng, Ali Zhu, Liqiao Ma, Weihong Li, Peng Yu, And Tao Zhu
The COVID-19 pandemic has greatly accelerated the application of mRNA technology, demonstrating its unique advantages over traditional biopharmaceutical and vaccine technology. However, mRNA instability in human physiological environments and inefficient in vivo delivery remain major barriers. mRNA chemical modifications and nano delivery systems are two key factors for in vivo applications. There is a need to summarize challenges for clinical. COVID-19 mRNA vaccine efficacy: BNT162b2 (Pfizer/BioNTech) 95% effective at 30 μg dose; mRNA-1273 (Moderna) 94.5% effective at 100 μg dose; both provide immunogenicity for at least 119 days after first vaccination. -.
mRNA is a promising cancer immunotherapy platform for vaccines, cytokines, costimulatory receptors, and therapeutic antibodies, but it is unstable, immunogenic, and poorly delivered in vivo. Safer and more efficient delivery systems are needed to improve mRNA stability, cellular uptake, endosomal escape, and tumor-site accumulation. PL1 LNPs delivering CD137 or OX40 mRNA to tumor-infiltrating T cells, combined with anti-OX40 antibody, showed more significant antitumor activity than anti-OX40 antibody alone in multiple tumor models. -.
Drug carriers are as important as drugs themselves, but clinical translation of polymeric nanocarriers (PNCs) remains limited by incomplete understanding of how carrier architecture and physicochemical properties affect loading, circulation, targeting, and release. The review addresses this gap by systematically linking structural varieties of PNCs and their physicochemical properties to drug delivery profiles, and by highlighting. Representative quantitative findings highlighted in the review: - Aspect ratio and uptake: cylindrical particles with aspect ratio 3 were internalized about 4-fold faster than aspect ratio 1 particles in HeLa cells,.
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.
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.
Folic acid (FA)-mediated active targeting improves nanocarrier tumor specificity but exposes targeting ligands to the immune system, causing rapid clearance and nonspecific uptake. Existing acid-labile benzoic-imine PEG sheddable systems are insufficiently stable at physiological pH. A more stable, tumor-triggered sheddable PEG stealth is needed to protect FA in circulation and expose it at tumor sites while also promoting intracellular drug. P1 micelles: \(D_h\) = 41 nm, narrow size distribution; stable at pH 7.4. - pH-triggered destabilization: At pH 6.5, size increased from 41 nm to 80 nm after 24 h; at pH 5.0, size increased to 627 nm. -.
Yao Y, Zhou Y, Liu L, Xu Y, Chen Q, Wang Y, Wu S, Deng Y, Zhang J, Shao A.
Conventional chemotherapy and targeted therapy are limited by systemic toxicity, poor tumor targeting, and multidrug resistance (MDR). Nanoparticle-based drug delivery offers improved pharmacokinetics, biocompatibility, enhanced permeability and retention (EPR), precise targeting, and potential to overcome resistance mechanisms such as efflux transporters, defective apoptosis, and hypoxia. NPs with diameters of 10–100 nm are generally suitable for cancer therapy; <10 nm are cleared by kidneys, >100 nm are cleared by phagocytes. - PEGylation reduces opsonization and immune clearance, prolonging.
Drug penetration into tumors is limited by abnormal vasculature and high interstitial pressure, and chemotherapy causes undesirable adverse effects including bone marrow and gastrointestinal toxicity. Nanotechnology-based drug delivery systems aim to reduce these adverse effects by enhancing penetration and selective drug retention in tumor tissues. A thorough knowledge of the physical properties (size, surface charge, shape, mechanical. 15 nm AuNPs showed highest accumulation in organs (liver, lung, spleen, kidney); only 15 and 50 nm AuNPs crossed the blood-brain barrier. - Renal clearance is rapid for particles <5–6 nm; clearance by liver and spleen.
Fam Sy, Chee Cf, Yong Cy, Ho Kl, Mariatulqabtiah Ar, Tan Ws.
Nanoparticles (NPs) interact extensively with plasma proteins after intravenous administration and are rapidly cleared by the mononuclear phagocyte system (MPS) or complement system, causing premature drug release at off-target sites. A stealth coating layer can improve blood circulation half-life by escaping immune recognition and clearance. Au-PEG10k: >95% still circulating 1 h after intravenous injection; Au-PEG750 did not show prolonged circulation. - Uncoated Au NPs and Au-PEG750: ~90% captured in liver and spleen after 1 h; Au-PEG10k: <5% at 1 h and.
CAR-T cell therapy relies mainly on retroviral/lentiviral vectors, which carry risks of carcinogenicity and complex manufacturing. PiggyBac transposon systems offer a safer, simpler non-viral alternative for stable transgene expression, but primary T lymphocytes are difficult to transfect efficiently. A polymeric nanomicelle carrier was developed to deliver PiggyBac transposon/transposase plasmids to human T cells. Nanomicelle properties: Blank micelles ~62.7 nm; polyplex at N/P 40 ~134.5 nm and +20.9 mV; complete DNA condensation at N/P 20; DTT released DNA. - Transfection at N/P 40: 24.5% ± 3.3% positive cells; viability 82.3% ±.
Ideal cancer nanomedicines need a stealth surface for prolonged circulation and tumor accumulation, but stealth surfaces often hinder cellular uptake. Conversely, cationic or targeting-ligand surfaces enhance uptake but cause rapid clearance and off-target interactions. This review addresses the central conflict between stealth and enhanced cellular uptake and summarizes surface-engineering strategies that integrate both properties in one system. Representative quantitative findings from cited studies: - MMP-2-activatable cell-penetrating peptides showed more than 10-fold increased cellular uptake after linker cleavage. - PolyHis-b-PEG micelles: DOX uptake by.
Biomaterials and nanoparticles (NPs) used for medical purposes often trigger immune recognition, inflammation, and rapid clearance by the reticuloendothelial system (RES)/mononuclear phagocyte system (MPS). PEGylation and cell-membrane camouflaging are common stealth strategies, but they have limitations, including anti-PEG immune responses. CD47, a “don’t-eat-me” signal, is emerging as an alternative stealth functionalization to improve. CD47-coated polystyrene beads reduced macrophage phagocytosis by 50% compared with CD47-free beads; anti-CD47 antibody abolished the effect. - CD47 immobilization on PVC tubing almost completely inhibited cell.
Polymeric nanocarriers such as dendrimers, micelles, nanoparticles, nanogels, nanocapsules, and vesicles are widely investigated for drug delivery, but their morphology, surface chemistry, and functionalization strongly influence drug loading, controlled release, and targeting. This review addresses the need for a systematic overview of how morphology and surface modifications of polymeric nanocarriers can improve controlled drug delivery and. Dendrimers: Drug loading in interior core or on branched surface; size range 1–100 nm (mostly <10 nm); pH-responsive DOX release from FA-PEG-PAMAM-DOX@IONPs; GA-PPI dendrimers enhanced liver cell targeting and minimized.
Ferrari, R.; Sponchioni, M.; Morbidelli, M.; Moscatelli, D
Many polymer-based nanoparticle formulations fail before or during clinical trials. This review identifies the key checkpoints a nanocarrier must satisfy after intravenous injection — biocompatibility, drug loading/release, storage stability, biodistribution, target selectivity, cellular internalization, and biodegradability — to improve the success rate of polymer-based anticancer nanomedicines. Size: Optimum intravenous NP size is 30–300 nm; >300 nm risks thrombosis and rapid clearance; <10 nm is renally excreted. - Marketed polymer NP formulations: Genexol-PM (2007, South Korea), Transdrug (2005, USA),.
Polymer–drug conjugates have achieved clinical success, especially PEG–protein conjugates, but translation of many conjugates—particularly polymer–small-molecule anticancer therapeutics—remains limited. This review addresses the need for rational design, better understanding of in vivo barriers, and identification of obstacles to clinical translation. Oncaspar: PEG–L-asparaginase half-life extended to 357 h vs 20 h for unmodified enzyme. - Mircera: PEG–epoetin beta half-life 134 h vs <25 h for other ESAs. - PK1: 15-fold improved plasma half-life and 17–77-fold.
Jayoung Kim, James G. Shamul, Sagar R Shah, Alyssa Shin, Ben J Lee, Alfredo Quiñones‐hinojosa, Jordan J. Green
Many anticancer small molecules have poor aqueous solubility, and verteporfin (VP) has mainly been used as a photodynamic therapy agent, which carries photosensitivity and delivery limitations. PBAE-based materials have been developed extensively for nucleic acid delivery but are less explored for non-genetic hydrophobic drug delivery. There is a need for biodegradable, pH-sensitive micelles that can encapsulate VP and potentially evade. CMC: PP1 micelles formed at 0.056 mg/mL. - Macrophage uptake: fVPM showed an 89% drop in cellular uptake percentage and a 5.6-fold drop in normalized geometric mean uptake compared with sVPM in RAW 264.7 macrophages. -.
Amphiphilic poly(amino acid)-based micelles are attractive for systemic drug delivery because they are biodegradable, biocompatible, have functional side groups, can load diverse drugs, and can exploit the EPR effect. However, low cargo capacity and poor stability in blood remain major barriers to clinical translation. This review summarizes the chemistry, drug-loading forces, in vitro/in vivo challenges, and strategies to improve loading and. Drug loading examples: PEG-b-PAsp-DOX conjugate DL 17%, 15–60 nm; PEG-b-PGlu-CDDP coordination DL 30%, ~30–40 nm; NK105 PTX DL 23%, ~85 nm; PEG-b-PGlu CPT-11 conjugate DL 20%, 20 nm; mPEG-b-PGlu DOX electrostatic DL.
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.
Cationic polymeric gene carriers are promising non-viral vectors, but their slow degradability and intracellular/tissue accumulation cause cytotoxicity. Bioreducible polymers containing disulfide linkages are attractive because they are stable extracellularly but degrade selectively in the reducing intracellular environment via thiol–disulfide exchange, triggered by high glutathione (GSH) levels. This review covers recent advances in. SS-PAED/RTP-VEGF produced 67-fold and 76-fold increases in VEGF expression under hypoxia vs normoxia in H9C2 cells; in a rabbit infarct model, VEGF expression was about 4-fold higher than RTP-Luc control and 2-fold.
siRNA has broad therapeutic potential, but clinical translation is limited by rapid nuclease degradation, poor accumulation in target tissues, and inability to cross cell membranes to reach the cytoplasm. Lipid nanoparticles containing ionizable amino lipids are the leading systemic delivery system for siRNA, with several formulations already in clinical trials. LNP siRNA systems are typically <100 nm; microfluidic mixing with PEG-lipid content from 0.5 to 5 mol% decreases diameter from ~100 nm to 25 nm, while encapsulation efficiency remains >95%. - Optimal ionizable lipid pKa.
Lipid-based nanocarriers such as liposomes and micelles can protect drugs, reduce nonspecific toxicity, and improve pharmacokinetics, but conventional formulations are limited by rapid clearance, poor targeting, and inefficient intracellular delivery. Engineering “multifunctional pharmaceutical nanocarriers” that combine longevity, targeting, stimuli-sensitivity, and imaging could significantly improve therapeutic and diagnostic protocols. Conventional liposomes: 50–80% of dose is captured by RES within 15–30 min after IV administration. - PEGylated liposomes: circulation half-life >20 h, with only 10–15% of dose captured by liver. - Micelles: typical.
Bioreducible polymers containing disulfide linkages are attractive gene-delivery carriers because they are stable in the oxidizing extracellular environment but degrade rapidly in the reducing intracellular cytosol via thiol–disulfide exchange, triggered by high glutathione (GSH) levels. This review addresses the need for carriers that combine extracellular stability, intracellular gene release, and reduced cytotoxicity, unlike hydrolytically. Reducibly cross-linked low-MW PEI (800 Da) with DSP or DTBP improved gene delivery to CHO cells; DTBP conjugates gave higher gene expression than DSP conjugates at equal N/P ratios due to amidine bond formation.
