Papers, explained in our own words

1. Current progress of self‑healing polymers for medical applications in tissue engineering

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.

2. Manipulating the function of tumor-associated macrophages by siRNA-loaded lipid nanoparticles for cancer immunotherapy

Nour Shobaki, Yusuke Sato, Yuichi Suzuki, Nana Okabe, Hideyoshi Harashima

Tumor-associated macrophages (TAMs) are largely M2-like and promote tumor growth, angiogenesis, metastasis, and immune suppression. There is a need for systemic delivery systems that can target TAMs and manipulate their pro-tumor functions with siRNA for cancer immunotherapy. Optimized CL4H6-LNPs had >90% siRNA encapsulation efficiency, neutral surface charge, and 90–100 nm size. - DSG-PEG2000 modification increased tumor accumulation 1.74-fold compared with DMG-PEG2000. - TAM uptake was.

3. Gene Delivery Nanoparticles to Modulate Angiogenesis

Jayoung Kim, Adam C. Mirando, Aleksander S. Popel, Jordan J. Green

Angiogenesis is normally balanced by pro- and anti-angiogenic factors, but imbalance leads to aberrant angiogenesis in ischemia, tissue regeneration, cancer, and neovascular age-related macular degeneration (wet AMD). Gene therapy is a promising strategy to introduce exogenous nucleic acids that express or silence target agents, thereby engineering neovascularization in both directions. Non-viral gene delivery nanoparticles have been widely investigated, but clinical translation remains hampered by safety, delivery efficiency, and therapeutic effect. This review consolidates key targets, non-viral nanoparticle approaches, and preclinical/clinical applications for angiogenesis modulation. --- - Ischemic limb: PEI/heparin-pVEGF nanoparticles increased capillary density >3-fold in mouse ischemic limb. PBAE-pVEGF-transfected HUVECs achieved 50% limb salvage vs 30% for lipo-pVEGF and 12.5% for PEI-pVEGF. - Myocardial infarction: WSLP-deliver

4. Stepwise pH-responsive nanoparticles containing charge-reversible pullulan-based shells and poly(β-amino ester)poly(lactic-co-glycolic acid) cores as carriers of anticancer drugs for combination therapy on he

Cong Zhang, Tong An, Dan Wang, Guoyun Wan, Mingming Zhang, Hemei Wang, Sipei Zhang, Rongshan Li, Xiaoying Yang, Yinsong Wang

Hepatocellular carcinoma (HCC) has poor prognosis and limited effective systemic therapy. Combination antiangiogenesis and chemotherapy with paclitaxel (PTX) and combretastatin A4 (CA4) is synergistic, but both drugs have poor solubility, lack tumor targeting, and cause systemic toxicity. A tumor microenvironment–responsive carrier is needed to co-deliver them selectively to HCC. Nanoparticle properties: PBAE/PLGA nanoparticles were ~120 nm; CAPL/PBAE/PLGA nanoparticles were ~178.1 nm with zeta potential −17.8 mV and a core–shell structure with 20–50 nm shell. - pH-responsive charge reversal: At.

5. In Vivo Delivery of miRNAs for Cancer Therapy: Challenges and Strategies

Yunching Chen, Dong-Yu Gao, Leaf Huang

miRNAs can simultaneously regulate multiple cancer-related genes, making them attractive therapeutic agents or targets. However, efficient, specific, and safe systemic delivery of therapeutic miRNAs in vivo remains a major challenge due to rapid degradation, poor tumor penetration, immunotoxicity, endosomal trapping, off-target effects, and saturation of miRNA-processing enzymes. This review discusses these barriers and current strategies to deliver miRNAs for cancer therapy without inducing toxicity. --- - Local let-7 delivery: intranasal lentiviral let-7a inhibited K-ras-dependent lung tumors; local synthetic let-7b reduced tumor size by 60–70% after four treatments at 3-day intervals. - Modified miR-143: systemic administration of passenger-strand-modified miR-143 produced 15% (low dose) to 50% (high dose) tumor growth inhibition in xenografted DLD-1 human colorectal tumors. - Neutral lipid delivery: systemic miR-34a or let-7 mimics

6. 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.

7. Genetic Engineering of Human Stem Cells for Enhanced Angiogenesis Using Biodegradable Polymeric Nanoparticles

Fan Yang, Seung-Woo Cho, Sun Mi Son, Said R. Bogatyrev, Deepika Singh, Jordan J. Green, Ying Mei, Sohyun Park, Suk Ho Bhang, Byung-Soo Kim, Robert Langer, Daniel G. Anderson

Stem cell therapy for angiogenesis is limited by insufficient expression of angiogenic factors and poor cell viability after transplantation. Viral gene delivery raises safety concerns, while non-viral methods often suffer from low transfection efficiency and toxicity. A safe, efficient, biodegradable polymeric nanoparticle system is needed to transiently engineer human stem cells to overexpress VEGF for therapeutic angiogenesis. In vitro VEGF: PBAE-transfected hMSCs/hESdCs secreted ~1–3-fold more VEGF than untransfected controls and ~1–2-fold more than Lipofectamine 2000 at day 4 (P < 0.05); viability 80–90%. - Subcutaneous model: Scaffolds.