The era of genetic medicine is rapidly unfolding, with major advances in tools for gene editing, silencing, and replacement. Gene editing machinery is versatile and can be delivered in the form of DNA (e.g., plasmids), RNA (e.g., mRNA and guide RNA) or directly in protein form as a ribonucleoprotein complex (RNP). Yet a fundamental challenge shared across these modalities remains: achieving safe, efficient and targeted intracellular delivery. In parallel with progress in the gene correction technologies, smart biomaterials are emerging as powerful platforms capable of overcoming the biological barriers that limit delivery. Lipid nanoparticles (LNPs) have gained remarkable momentum, enabling effective local and systemic administration and driving the first generation of genetic medicines into clinical trials. Beyond LNPs, a diverse landscape of smart materials, including programmable polymers, inorganic nanomaterials, biomimetic vesicles, virus-like particles and hybrid systems, offers complementary advantages for tissue targeting and controlled release. In this review, we summarise recent advances across these material classes, with a focus on design principles that enhance cellular uptake and enable precise intracellular release of gene editing cargos. We highlight applications spanning ex vivo cell engineering to in vivo correction of genetic diseases, and we discuss key translational considerations, including safety, manufacturability, and regulatory expectations. By integrating mechanistic understanding with clinical perspective, this review aims to guide the rational development of next-generation smart materials that will unlock the full therapeutic potential of gene-editing technologies.
IntroductionCitrus unshiu Markovich (CUM) is a Korean traditional medicine with proven therapeutic activities for various diseases. However, the major constraint associated with it is its poor solubility and bioavailability, thus requiring high dosages for cancer treatment. This study aimed to evaluate the anticancer activities of CUM peel extract.MethodsAn extract of CUM fruit skin peel was prepared and then subjected to analysis for total phenolic and flavonoid compounds and antioxidant activity. In silico bioactivity prediction analysis was performed using various bioinformatic tools. The CUM nanoparticles (NPs) was synthesized, and their anticancer activity against HeLa cancer cells was evaluated. The regulatory pathway investigation and protein-protein network associations were also carried out.ResultsThe total phenolic and flavonoid contents were found to be 53.93 mg/g eq. of GAE and 7.96 μg/g, respectively. Citrus unshiu Markovich (CUM) peel extract exhibited the highest radical scavenging activities; with 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) ABTS were found to be 99.96% and 98.60%, respectively. The ferric reducing antioxidant power (FRAP) assay yielded a value of 335.08 + 4.88 µmol FeSO4/L. Field-emission scanning electron microscopy (FE-SEM) and high-resolution transmission electron microscopy (HR-TEM) revealed the CUM NPs were well dispersed and uniform, with an average diameter of 40–60 nm. Additionally, the Fourier-transform infrared spectroscopy Fourier transform infrared (FTIR) spectrum of CUM NPs showed strong peaks at 3,545, 2,938, 2,917, and 3,283 cm−1 attributed to different phenolic compounds. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay demonstrated that CUM NPs induced cytotoxicity against HeLa cells at an effective concentration of 30 μg/mL. Fluorescence-activated cell sorting (FACS) analysis revealed an apoptotic cell death of 54.4% in CUM NPs treated cells, compared with 16.5% in cells treated with free CUM. Furthermore, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis of candidate gene expression demonstrated significant (p < 0.05) downregulation of interleukin-6 (IL-6), B-cell lymphoma 2 (Bcl-2), and matrix metalloproteinase-9 (MMP-9), and the genes Caspase-9, Bcl-2- associated X protein (Bax), and tumor protein p53 revealed significant (p < 0.05) upregulation in CUM NPs treated cells as compared to control groups.DiscussionPhytochemical and antioxidant properties of CUM peel extract and its nano-formulated particles were demonstrating promising in-vitro anticancer activity against HeLa cervical cancer cells. These findings highlight the potential of CUM NPs as a promising nanotechnology-based approach for further exploration in cancer research and provide a foundation for further investigate their therapeutic applications.
Over the past decade, hydrogels have garnered significant interest in drug delivery, wound healing, and tissue engineering because of their high water content, biocompatibility, and tunable physicochemical properties. A bioactive amino acid, L-theanine, is known for its neuroprotective, antioxidant, and anticancer properties. The objective of this study is to design and evaluate a composite hydrogel system to encapsulate and release L-theanine over time. Three different types of hydrogels (PVP-G HG, PVP-G@Th HG, and PVP-G@Th-NP HG) were prepared via a hybrid crosslinking approach involving glutaraldehyde chemical gelation and freeze-thaw physical texturing, and characterized by SEM, FTIR, and PXRD, confirming successful formation of the hydrogel and drug encapsulation. The gel fraction of the hydrogel was evaluated by measuring the amount of crosslinking inside the hydrogel as 74.576% ± 1.03%. From the formulations, PVP-G@Th HG exhibited higher swelling capacity in water (1033.53% ± 9.25%). Weight loss was seen during the in vitro degradation period of 7 days, where PVP-G HG, PVP-G@Th HG, and PVP-G@Th-NP HG were degraded by 34.32% ± 0.58%, 40.71% ± 0.76%, and 45.32% ± 0.71%, respectively. The drug release studies for 48 h showed sustained L-theanine release from PVP-G@Th HG (69.48%) and PVP-G@Th-NP HG (42.23%), with the Higuchi model (R2 = 0.996) and the Korsmeyer-Peppas model (R2 = 0.973), respectively. The antioxidant activity evaluated by DPPH showed a good radical scavenging effect in which the highest activity was observed for PVP-G@Th HG (80.71% ± 0.92%) at 450 min, followed by PVP-G@Th-NP HG (75.83% ± 1.23%). The nanoparticle (NP)-loaded L-theanine (Th) hydrogel (HG) (PVP-G@Th-NP HG) exhibited a slower and more controlled release profile than the directly loaded hydrogel (PVP-G@Th HG), reflecting more regulated release kinetics rather than a greater extent of release. This formulation may therefore offer a more sustained delivery profile suitable for further evaluation in controlled drug-delivery applications.
This study investigated the biological effects of size-and shape-controlled silver nanoparticles on HCT-116 colon carcinoma cells. Silver decahedral nanoparticles (AgNDs), with average diameters of 41 nm and 90 nm, were synthesized photochemically, while silver pentagonal nanorods (AgNRs), with a length of approximately 90 nm, were synthesized thermochemically. UV-vis spectroscopy, transmission electron microscopy (TEM), and scanning electron microscopy were used to confirm and characterize the synthesized nanoparticles. The cytotoxic effects of the nanoparticles were evaluated using a viability assay (MTT assay) at 72 h following exposure to a range of concentrations. Results demonstrated that nanoparticle size and shape influence cellular responses. Among the AgNDs, the 41 nm AgNDs were more cytotoxic than the 90 nm AgNDs, reflected by their lower IC50 value, demonstrating a size-dependent difference in cytotoxicity. However, 90 nm AgNRs displayed even greater cytotoxicity despite their larger length dimensions, suggesting that particle geometry strongly influences nanoparticle-cell interactions and biological activity. To further investigate potential molecular responses associated with nanoparticle-induced cytotoxicity, Western blot analysis was performed to evaluate the expression of key proteins associated with apoptotic pathways, proliferation, and survival signaling cascades. Exploratory analysis showed treatment-associated differences in these proteins, including a higher relative p53 signal in the 90 nm AgNR-treated condition. As these observations were obtained from a single biological experiment, they provide preliminary mechanistic context and require independent quantitative validation. Collectively, these findings demonstrate that nanoparticle size and morphology play critical roles in mediating the anticancer activity of silver nanoparticles and emphasize the importance of precise structural development when designing nanoparticle-based therapeutic strategies. These findings shed new light on nanoparticles-based therapeutics: To optimize the efficacy of these approaches, nanoparticles geometry should be carefully designed, taking into consideration the size and shape of nanoparticles.
