RESUMEN
One of the primary global health concerns is the increase in antimicrobial resistance. Polymer chemistry enables the preparation of macromolecules with hydrophobic and cationic side chains that kill bacteria by destabilizing their membranes. In the current study, macromolecules are prepared by radical copolymerization of caffeine methacrylate as the hydrophobic monomer and cationic- or zwitterionic-methacrylate monomers. The synthesized copolymers bearing tert-butyl-protected carboxybetaine as cationic side chains showed antibacterial activity toward Gram-positive bacteria (S. aureus) and Gram-negative bacteria (E. coli). By tuning the hydrophobic content, we prepared copolymers with optimal antibacterial activity against S. aureus, including methicillin-resistant clinical isolates. Moreover, the caffeine-cationic copolymers presented good biocompatibility in a mouse embryonic fibroblast cell line, NIH 3T3, and hemocompatibility with erythrocytes even at high hydrophobic monomer content (30-50%). Therefore, incorporating caffeine and introducing tert-butyl-protected carboxybetaine as a quaternary cation in polymers could be a novel strategy to combat bacteria.
RESUMEN
Photothermal/photodynamic therapies (PTT/PDT) are multimodal approaches employing near-infrared (NIR) light-responsive photosensitizers for cancer treatment. In the current study, IR-775, a hydrophobic photosensitizer, was used in combination with a polyphenols (p)-rich ethyl acetate extract from Terminalia chebula to treat cancer. IR-775 dye and polyphenols were encapsulated in a poly(lactic acid) polymeric nanosystem (PpIR NPs) to increase the cell bioavailability. The hydrodynamic diameter of PpIR NPs is 142.6 ± 2 nm and exhibited physical stability. The nanosystem showed enhanced cellular uptake in a lung cancer cell line (A549). Cell cytotoxicity results indicate that PpIR NPs showed more than 82.46 ± 3% cell death upon NIR light treatment compared to the control groups. Both PDT and PTT generate reactive oxygen species (ROS) and cause hyperthermia, thereby enhancing cancer cell death. Qualitative and quantitative analyses have depicted that PpIR NPs with NIR light irradiation have decreased protein expression of HSP70 and PARP, and increased γ-H2AX, which collectively lead to cell death. After NIR light irradiation, the relative gene expression patterns of HSP70 and CDK2Na were also downregulated. Further, PpIR NPs uptake has been studied in 3D cells and in ovo bioimaging in zebrafish models. In conclusion, the PpIR NPs show good cancer cell cytotoxicity and present a potential nanosystem for bioimaging.
Asunto(s)
Hipertermia Inducida , Nanopartículas , Neoplasias , Fotoquimioterapia , Terminalia , Animales , Polifenoles/uso terapéutico , Fotoquimioterapia/métodos , Terapia Fototérmica , Hipertermia Inducida/métodos , Pez Cebra , Nanopartículas/uso terapéutico , Fármacos Fotosensibilizantes/farmacología , Neoplasias/tratamiento farmacológicoRESUMEN
This study reports a hybrid lipo-polymeric nanosystem (PDPC NPs) synthesized by a modified hydrogel-isolation technique. The ability of the nanosystem to encapsulate hydrophilic and hydrophobic molecules has been demonstrated, and their enhanced cellular uptake has been observed in vitro. The PDPC NPs, surface coated with gold by in situ reduction of chloroauric acid (PDPC-Au NPs), showed a photothermal transduction efficacy of â¼65%. The PDPC-Au NPs demonstrated an increase in intracellular ROS, triggered DNA damage and resulted in apoptotic cell death when tested against breast cancer cells (MCF-7). The disintegration of PDPC-Au NPs into smaller nanoparticles with near-infrared (NIR) laser irradiation was understood using transmission electron microscopy imaging. The lipo-polymeric hybrid nanosystem exhibited plasmon-enhanced fluorescence when loaded with IR780 (a NIR dye), followed by surface coating with gold (PDPC-IR-Au NPs). This paper is one of the first reports on the plasmon-enhanced fluorescence within a nanosystem by simple surface coating of Au, to the best of our knowledge. This plasmon-enhanced fluorescence was unique to the lipo-polymeric hybrid system, as the same was not observed with a liposomal nanosystem. The plasmon-enhanced fluorescence of PDPC-IR-Au NPs, when applied for imaging cancer cells and zebrafish embryos, showed a strong fluorescence signal at minimal concentrations of the dye. The PDPC-IR-Au NPs were also applied for photothermal therapy of breast cancer in vitro and in vivo, and the results depicted significant therapeutic benefits.
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Neoplasias de la Mama , Oro , Animales , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/terapia , Línea Celular Tumoral , Femenino , Oro/química , Oro/farmacología , Humanos , Fototerapia/métodos , Terapia Fototérmica , Polímeros/química , Polímeros/farmacología , Pez CebraRESUMEN
Metastasis is one of the predisposing factors for cancer-related mortalities worldwide. Patients with advanced cancers (stage IV) receive palliative care with minimal possibility of achieving complete remission. Antibody-based therapeutic modalities are capable of targeting tumors that are confined to a particular location but are ineffective in targeting distant secondary tumors. In the current study, we have developed a smart nano-transforming hydrogel (NTG) that transforms in situ to polymeric nanoparticles (PA NPs) of 100-150 nm when injected subcutaneously. These nanoparticles targeted the primary and secondary metastatic tumors for up to â¼5 and â¼3 days, respectively. The in situ-formed PA NPs also demonstrated a pH-responsive drug release resulting in about â¼80% release within 100 h at 5.8 pH. When tested in vivo, substantial inhibition of lung metastases was observed compared to chemotherapy, thus demonstrating the efficiency of nanotransforming hydrogels in targeting and inhibiting primary and secondary metastatic tumors.
Asunto(s)
Antibióticos Antineoplásicos/farmacología , Materiales Biocompatibles/química , Doxorrubicina/farmacología , Hidrogeles/química , Neoplasias Pulmonares/tratamiento farmacológico , Melanoma Experimental/tratamiento farmacológico , Nanopartículas/química , Terapia Fototérmica , Animales , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/química , Materiales Biocompatibles/administración & dosificación , Línea Celular , Doxorrubicina/administración & dosificación , Doxorrubicina/química , Femenino , Oro/administración & dosificación , Oro/química , Hidrogeles/administración & dosificación , Inyecciones Subcutáneas , Liposomas/administración & dosificación , Liposomas/química , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Melanoma Experimental/patología , Melanoma Experimental/secundario , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Nanopartículas/administración & dosificación , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
Photodynamic/photothermal therapy (PDT/PTT) that deploys a near-infrared responsive nanosystem is emerging to be a promising modality in cancer treatment. It is highly desirable to have a multifunctional nanosystem that can be used for efficient tumor targeting and inhibiting metastasis/recurrence of cancer. In the current study, self-assembled chlorophyll-rich fluorosomes derived from Spinacia oleracea were developed. These fluorosomes were co-assembled on a polydopamine core, forming camouflaged nanoparticles (SPoD NPs). The SPoD NPs exhibited a commingled PDT/PTT (i.e., interdependent PTT and PDT) that inhibited both normoxic and hypoxic cancer cell growth. These nanoparticles showed stealth properties with enhanced physiological stability and passive tumor targeting. SPoD NPs also exhibited tumor suppression by synergistic PTT and PDT. It also prevented lung metastasis and splenomegaly in tumor-bearing Balb/c mice. Interestingly, treatment with SPoD NPs also caused the suppression of secondary tumors by eliciting an anti-tumor immune response. In conclusion, a co-assembled multifunctional nanosystem derived from S. oleracea showed enhanced stability and tumor-targeting efficacy, resulting in a commingled PDT/PTT effect.