Papers, explained in our own words

1. Recent progress in targeted delivery vectors based on biomimetic nanoparticles

Chen L, Hong W, Ren W, Xu T, Qian Z, He Z.

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.

2. Targeted drug delivery strategies for precision medicines

Mandana T. Manzari, Yosi Shamay, Hiroto Kiguchi, Neal Rosen, Maurizio Scaltriti, And Daniel A. Heller

Precision medicine has transformed cancer therapy by enabling molecular profiling and optimized drug design, but clinical translation of many precision therapeutics is hindered by pharmacological limitations, including toxicities and drug resistance. Drug delivery materials can modulate a drug’s pharmacokinetics, biodistribution, and toxicity without compromising its molecular target engagement, offering a route to improve the therapeutic index. Kinase inhibitor landscape: More than 50 small-molecule protein kinase inhibitors have been FDA-approved, with the majority developed as targeted cancer therapeutics. - Dose-limiting toxicity example: In a phase I trial.

3. Peptide functionalized liposomes for receptor

Matthew R. Aronson, Scott H. Medina, Michael J. Mitchell

Most clinically approved cancer therapies are potent and toxic small molecules limited by severe off-target toxicities and poor tumor-specific localization. Liposomal encapsulation reduces toxicity, but reliance on passive targeting via the enhanced permeability and retention (EPR) effect leaves unresolved issues such as heterogeneous tumor accumulation. Peptide-functionalized liposomes offer an active targeting strategy for receptor-mediated. TfR-targeting T7: D-enantiomer T7 showed increased binding affinity over L-T7 and transferrin; T7-liposomes loaded with docetaxel significantly reduced tumor growth in mice. T7-quercetin liposomes increased cytotoxicity.

4. Role of Apolipoprotein- and Vitronectin-Enriched Protein Corona on Lipid Nanoparticles for In Vivo Targeted Delivery and Transfection of Oligonucleotides in Murine Tumor Models

Dongyu Chen, Neha Parayath, Shanthi Ganesh, Weimin Wang, Mansoor Amiji

The protein corona that forms on lipid nanoparticles (LNPs) after systemic administration can alter their biological identity, but its impact on tumor delivery is not well understood. This study aimed to determine whether LNP formulation composition and surface charge can manipulate the protein corona and thereby affect in vitro transfection, in vivo biodistribution, and tumor-specific delivery of oligonucleotides. 20 LNPs were prepared with similar size (~80–100 nm), PDI, and ~90% encapsulation; DC-CHOL LNPs had positive zeta potential and were smaller (~70 nm). - Apolipoproteins (ApoE, ApoA4, ApoB) were major corona proteins for.

5. Role of Surface Chemistry on Serum Protein Corona-Mediated Cellular Delivery and Gene Silencing with Lipid Nanoparticles

Dongyu Chen, Shanthi Ganesh, Weimin Wang, Mansoor Amiji

Protein corona formation in biological fluids can alter nanoparticle cellular uptake, transfection, and gene silencing, but the relationship between LNP surface chemistry and corona-mediated delivery is incompletely understood. This study examined how PEG lipid chain length and PEG molar ratio affect protein corona composition and siRNA delivery in hepatocellular carcinoma cells. All four LNPs had similar size (~90 nm), PDI (<0.1), and encapsulation efficiency (>90%); zeta potential was near neutral. - Surface PEG molar ratio by ¹H NMR was approximately 1.9:1.0:2.0:1.0 for F1:F2:F3:F4, matching.

6. Engineering Nanoparticles for Targeted Delivery of Nucleic Acid Therapeutics in Tumor

Yao Xiao, Kun Shi, Ying Qu, Bingyang Chu, Zhiyong Qian

In the past 10 years, many clinical nano-gene therapy trials have been discontinued due to poor efficacy and serious side effects. There is a critical need to design suitable gene delivery systems that can protect nucleic acids, enhance transfection efficiency, penetrate deep into tumors, and remain stable and safe during blood circulation while accumulating at tumor sites. --- - CALAA-01: Polymer-based NP with transferrin targeting and siRNA against RRM2; dose-dependent tumor accumulation and target inhibition; trial terminated due to 21% adverse event rate from drug instability. - siG12D LODER: PLGA matrix implanted into pancreatic tumors; slow release of siRNA against KRAS G12D; passed phase 1/2a with good anticancer effects. - TKM-080301: SNALP with siRNA against PLK1; evaluated in phase I/II for gastrointestinal neuroendocrine tumors and adrenocortical carcinoma. - PEI-HNPs for CRISPR/Cas9: Achieved up to 60% Cas9 transfection effi

7. A novel MUC1 aptamer-modified PLGA-epirubicin-PβAE-antimir-21 nanocomplex platform for targeted co-delivery of anticancer agents in vitro and in vivo

Amirhossein Bahreyni, Mona Alibolandi, Mohammad Ramezani, Atefeh Sarafan Sadeghi, Khalil Abnous, Seyed Mohammad Taghdisi

Conventional chemotherapy for breast and colon cancers suffers from low specificity, rapid drug clearance, and severe toxic side effects on healthy tissues, while chemoresistance and metastasis remain major causes of cancer-related mortality. There is an unmet need for targeted delivery systems that can co-deliver chemotherapeutic agents with oligonucleotide-based therapeutics (e.g., miRNA inhibitors) to enhance efficacy and reduce off-target. Epi Release Profile: - ~80% Epi released at pH 5.5 (tumor tissue/lysosomal pH) after 72 h - ~28% Epi released at pH 7.4 (physiological blood pH) after 72 h - Demonstrates pH-responsive release mediated by PβAE.

8. T cell-targeting nanoparticles focus delivery of immunotherapy to improve antitumor immunity

Daniela Schmid, Chun Gwon Park, Christina A. Hartl, Nikita Subedi, Adam N. Cartwright, Regina Bou Puerto, Yiran Zheng, James Maiarana, Gordon J. Freeman, Kai W. Wucherpfennig, Darrell J. Irvine, Michael S. Goldberg

Systemic immune stimulation for cancer immunotherapy is associated with autoimmune-type pathologies, as the doses required to break immune tolerance can invoke undesired host-vs.-host effects. Targeting endogenous immune cell subsets in the circulation—which actively migrate into tumors—could concentrate immunomodulatory drugs on tumor-reactive effector cells, improving both efficacy and safety compared to administration of free drugs or direct. ### Nanoparticle Characterization | Parameter | Uncoated NPs | Isotype NPs | CD8a NPs | |---------------|------------------|-----------------|--------------| | Size (nm) | 267 ± 8 | 269 ± 8 | 273 ± 8 | | Antibody.

9. Liposomal Formulations in Clinical Use: An Updated Review

Liposomes are the first nano drug delivery systems successfully translated into clinical use, but many formulations still face limitations in biodistribution, toxicity, stability, and target selectivity. An updated review was needed to summarize liposome technologies, marketed clinical products, formulation aspects, and ongoing clinical trials. Doxil was the first FDA-approved PEGylated liposomal nano-drug in 1995. It has 80–100 nm vesicles, >90% doxorubicin encapsulation, clearance of 0.1 L/h vs 45 L/h for free drug, volume of distribution 4 L vs 254 L, and.

10. Targeted Delivery of MicroRNA125a-5p by Engineered Lipid Nanoparticles for the Treatment of HER2 Positive Metastatic Breast Cancer

Stephen L. Hayward, David M. Francis, Parviz Kholmatov, Srivatsan Kidambi

miRNA-based therapeutics are limited by instability, poor cellular uptake, lack of targeting, and potential immune activation. No nonviral miRNA delivery strategy had been explored as a standalone treatment for HER2-positive metastatic breast cancer. HA-LNP uptake was significantly higher than naked FITC-dextran and highest in metastatic 21MT-1 cells, correlating with CD44 expression. - HA pre-treatment reduced HA-LNP uptake by 55%, supporting CD44-mediated.

11. 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 ±.

12. Strategies on the nuclear-targeted delivery of genes

Jing Yao, Ying Fan, Yuanke Li, And Leaf Huang

Non-viral gene delivery systems are safer than viral vectors but are highly inefficient at nuclear delivery. Only ~10–20% of applied plasmid DNA enters targeted cells, and only ~1–5% of the applied dose reaches the nucleus. The nuclear envelope is a major barrier to transgene delivery, and there is a need for “smart” non-viral vectors that can overcome multiple extracellular and intracellular barriers—especially nuclear transport—to enhance gene. Baseline inefficiency of non-viral vectors: Only 10–20% of applied plasmid DNA enters targeted cells, and only 1–5% enters the nucleus. - NLS enhancement: Addition of NLSs increased luciferase reporter gene expression.

13. E-selectin liposomal and nanotube-targeted delivery of doxorubicin to circulating tumor cells

Hughes Ad, King Mr

Metastasis is the leading cause of cancer mortality, and circulating tumor cells (CTCs) are key to metastatic spread. Doxorubicin (DXR) is effective but systemically toxic and nonspecific. A targeted delivery system was needed to capture and kill CTCs under physiologically relevant flow while reducing off-target toxicity. Liposome characterization: L-DXR 106.3 ± 5.9 nm, ζ = −24.56 ± 6.34 mV; PEG L-DXR 111.5 ± 6.4 nm, ζ = −8.49 ± 5.85 mV; ES-PEG L-DXR 143.7 ± 11.2 nm, ζ = −13.12 ± 6.28 mV. DXR loading >95%; minimal leakage over 39 days. -.

14. Polyethylenimine-grafted copolymer of poly(L-lysine) and poly(ethylene glycol) for gene delivery

Dai J, Zou S, Pei Y, Cheng D, Ai H, Shuai X

PEI is an effective gene carrier but high-molecular-weight PEI is nonbiodegradable and cytotoxic; PLL is biodegradable but lacks proton-buffering capacity, has low transfection efficiency, and is also cytotoxic. A vector combining the complementary strengths of PEI and PLL is needed. Cytotoxicity: At 100 µg/mL, PPL left 41% cell viability, while PPI3 left 78%; PPI1 and PPI2 left 51% and 56%, respectively. At 22 µg/mL nitrogen concentration, viability was 23% for PPL vs 78% for PPI3. - Buffering:.

15. Targeted Gene Silencing Using RGD-Labeled Chitosan Nanoparticles

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.

16. Polymeric nanoparticles for cancer therapy

Parveen, S.; Sahoo, S. K

Conventional cancer chemotherapy suffers from poor tumor selectivity, high required doses, systemic toxicity, rapid drug elimination, and multidrug resistance. Polymeric nanoparticles (NPs) are reviewed as a strategy to improve targeted delivery, controlled release, and therapeutic efficacy while reducing adverse effects. Transferrin-conjugated paclitaxel NPs: Direct intratumoral injection in a subcutaneous prostate cancer mouse model produced complete tumor regression at a single TX dose of 4 mg/kg, with greater survival than TX-NPs or.

17. Selective targeting of antibody-conjugated nanoparticles to leukemic cells and primary T-lymphocytes

Norbert Dinauer, Sabine Balthasar, Carolin Weber, Jörg Kreuter, Klaus Langer, Hagen Von Briesen

Antibody-based therapeutics have shown promise in targeting specific cell types, but their efficacy can be enhanced by conjugation to drug carriers. Nanoparticles as drug carriers offer advantages including high drug loading capacity, controlled release, and protection from degradation. However, achieving selective cellular uptake via receptor-mediated endocytosis requires targeted delivery systems. A nanoparticle platform that can be. ### Nanoparticle Characterization & Antibody Coupling | Parameter | Value | |---------------|-----------| | Nanoparticle size | ~211 nm | | NAv binding capacity | 7.36 × 10⁻¹⁰ mol NAv/mg NPs | | Anti-CD3 binding |.