Adamoski, D. | Search bioRxiv

bioRxiv2023

Iron Oxide Nanoparticles Coated with Biodegradable Block-Copolymer PDMAEMA-b-PMPC and Functionalized with Aptamer for HER2 Breast Cancer Cell Identification

Hybrid nanoparticles have shown promise in biomedical applications; however, their seamless integration into clinical settings remains challenging. Here, we introduce a novel metal oxide polymer hybrid nanoparticle (NP) with a high affinity for nucleic acids. Iron oxide nanoparticles (IONP) were initially synthesized via the co-precipitation method and subjected to comprehensive characterization. Subsequently, block copolymers were synthesized using the Reversible Addition-Fragmentation Chain Transfer (RAFT) technique, employing the zwitterionic PMPC (Poly (2 Methacryloyloxyethyl Phosphorylcholine)) and the cationic PDMAEMA (Poly(2 (Dimethylamino) Ethyl Methacrylate)) with varying degrees of polymerization. In vitro cytotoxicity studies demonstrated the biocompatibility of the synthesized nanoparticles, with no observed toxicity up to a concentration of 150 {micro}g/mL. The cationic polymer PDMAEMA facilitated the facile coating of IONP, forming the IONPP complex, consisting of a 13.27 metal core and a 3.1 nm block-copolymer coating. Subsequently, the IONPP complex was functionalized with a DNA aptamer specifically targeting the human epidermal growth factor receptor 2 (HER2) in breast cancer, forming IONPPP. The block-copolymer exhibited an EC50 of 7.07 {micro}g/mL and demonstrated enhanced recognition efficiency in HER2-amplified SKBR3 cells. Our study presents a comprehensive IONPPP characterization capable of binding short DNA sequences and targeting proteins such as HER2. This newly developed nanoparticle holds significant potential for cancer cell identification and isolation, offering promising prospects in cancer research and clinical applications. 1. Statement of significanceDespite recent advancements in biomedical research, developing sensitive and specific tools for recognizing biological motifs, such as cell receptors and proteins in complex biological solutions, remains a challenge. Furthermore, current approaches often rely on complex biological derivatives like antibodies, lacking a cost-effective delivery strategy. Our study proposes creating and characterizing a novel hybrid metal oxide polymer nanoparticle named IONPPP, functionalized with a DNA aptamer designed to recognize HER2-positive cells. HER2 is a clinically actionable marker for gastric, gastroesophageal, and, particularly, breast cancers. This unique combination of a metal core with an external polymeric structure offers the potential for identification, isolation, and even theragnostic applications, benefiting from its low toxicity and high specificity. 2. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/543859v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@ff36a9org.highwire.dtl.DTLVardef@15da74corg.highwire.dtl.DTLVardef@1929c6aorg.highwire.dtl.DTLVardef@5afd2f_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2022

Different biological effects of exposure to far-UVC (222 nm) and near-UVC (254 nm) irradiation

Ultraviolet C (UVC) light has long been used as a sterilizing agent, primarily through devices that emit at 254 nm. Depending on the dose and duration of exposure, UV 254 nm can cause erythema and photokeratitis and potentially cause skin cancer since it directly modifies nitrogenated nucleic acid bases. Filtered KrCl excimer lamps (emitting mainly at 222 nm) have emerged as safer germicidal tools and have even been proposed as devices to sterilize surgical wounds. All the studies that showed the safety of 222 nm analyzed cell number and viability, erythema generation, epidermal thickening, the formation of genetic lesions such as cyclobutane pyrimidine dimers (CPDs) and pyrimidine-(6-4)-pyrimidone photoproducts (6-4PPs) and cancer-inducing potential. Although nucleic acids can absorb and be modified by both UV 254 nm and UV 222 nm equally, compared to UV 254 nm, UV 222 nm is more intensely absorbed by proteins (especially aromatic side chains), causing photooxidation and cross-linking. Here, in addition to analyzing DNA lesion formation, for the first time, we evaluated changes in the proteome and cellular pathways, reactive oxygen species formation, and metalloproteinase (MMP) levels and activity in full-thickness in vitro reconstructed human skin (RHS) exposed to UV 222 nm. We also performed the longest (40 days) in vivo study of UV 222 nm exposure in the HRS/J mouse model at the occupational threshold limit value (TLV) for indirect exposure (25 mJ/cm2) and evaluated overall skin morphology, cellular pathological alterations, CPD and 6-4PP formation and MMP-9 activity. Our study showed that processes related to reactive oxygen species and inflammatory responses were more altered by UV 254 nm than by UV 222 nm. Our chronic in vivo exposure assay using the TLV confirmed that UV 222 nm causes minor damage to the skin. However, alterations in pathways related to skin regeneration raise concerns about direct exposure to UV 222 nm.

cell biology↗