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Purpose: Polydopamine nanoparticles (PDA NPs) have great potential in medicine. Their applications being widely investigated in cancer therapy, imaging, chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), and tissue repair. The aim of our study was to assess the in vivo toxicity and changes in oxidative stress biomarkers in organs of animals treated with mesoporous PDA NPs modified with iron (MPDAFe NPs), coated with the cancer cell membrane and loaded with doxorubicin (DOX), and subsequently subjected to PTT., Methods: Liver and kidney homogenates were obtained from BALB/c nude mice with xenograft HepG2 human hepatoma cells, treated with iron modified mesoporous PDA nanoparticles, coated with the cancer cell membrane and loaded with doxorubicin (MPDAFe@DOX@Mem NPs), and subjected to PTT. These samples were used for histological evaluation and measurement of oxidative stress biomarkers, including total protein (TP), reduced glutathione (GSH), nitric oxide (NO), S-nitrosothiols (RSNO), thiobarbituric acid reactive substances (TBARS), trolox equivalent antioxidant capacity (TEAC), catalase (CAT), glutathione S-transferase (GST), and superoxide dismutase (SOD)., Results: In the kidney, MPDAFe@DOX@Mem NPs in combination with PTT increased GSH (43%), TBARS (32%), and CAT (27%), while SOD decreased by 20% compared to the control group. Additionally, CAT activity in the liver increased by 79%., Conclusion: Significant differences in oxidative stress parameters and histological changes after administration with MPDAFe@DOX@Mem NPs and PTT were observed in the kidneys, showing more pronounced changes than the liver, indicating potential kidney toxicity. Our research provides insights into oxidative stress and possible toxic effects after in vivo administration of mesoporous PDA NPs combined with chemotherapy-photothermal therapy (CT-PTT), which is extremely important for their future applications in anticancer therapies., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Szukalska et al.)

Cancer remains a leading cause of mortality worldwide, necessitating the development of innovative therapeutic approaches. Nanoparticle-based drug delivery systems have garnered significant interest due to their multifunctionality, offering the potential to enhance cancer treatment efficacy and improve patient tolerability. Membrane-coated drug delivery systems hold great potential for enhancing the therapeutic outcome of nanoparticle-based anticancer therapies. In this study, we report the synthesis of multifunctional iron-functionalized mesoporous polydopamine nanoparticles (MPDAFe NPs). These nanoformulations demonstrate substantial potential for combining efficient drug delivery and magnetic resonance imaging (MRI) and showcase the advantages of biomimetic coating with tumor cell-derived membranes. This coating confers prolonged circulation and improved the targeting capabilities of the nanoparticles. Furthermore, comprehensive biosafety evaluations reveal negligible toxicity to normal cells, while the combined chemo- and phototherapy exhibited significant cytotoxicity towards cancer cells. Additionally, the photothermal effect evaluation highlights the enhanced cytotoxicity achieved through laser irradiation, showcasing the synergistic effects of the nanomaterials and photothermal therapy. Importantly, our chemotherapeutic effect evaluation demonstrates the superior efficacy of doxorubicin-loaded MPDAFe@Mem NPs (cancer cell membrane-coated MPDAFe NPs) in inhibiting cancer cell viability and proliferation, surpassing the potency of free doxorubicin. This study comprehensively investigates theranostic, membrane-coated drug delivery systems, underlining their potential to increase the efficacy of cancer treatment strategies. The multifunctional nature of the iron-functionalized polydopamine nanoparticles allows for efficient drug delivery and imaging capabilities, while the biomimetic coating enhances their biocompatibility and targeting ability. These findings contribute valuable insights towards the development of advanced nanomedicine for improved cancer therapeutics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Polydopamine (PDA)-based nanostructures are used for biomedical purposes. A hybrid drug nanocarrier based on a PDA decorated with polyamidoamine (PAMAM) dendrimers G 3.0 (DG3) followed by a connection with glycol (PEG) moieties, folic acid (FA), and drug doxorubicin (DOX) was used for combined chemo- and photothermal therapy (CT-PTT) of liver cancer. Oxidative stress plays a crucial role in the development of cancer, and PDA seems to have the ability to both donate and accept electrons. We investigated oxidative stress in organs by evaluating oxidative stress markers in vivo. In the liver, the level of reduced glutathione (GSH) was lower and the level of Trolox equivalent antioxidant capacity (TEAC) was higher in the group receiving doxorubicin encapsulated in PDA nanoparticles with phototherapy (PDA@DG3@PEG@FA@DOX + PTT) compared to the control group. The concentration of thiobarbituric acid reactive substances (TBARS) in livers, was higher in the group receiving PDA coated with PAMAM dendrimers and functionalized with PEG and FA (PDA@DG3@PEG@FA) than in other groups. Markers in the brain also showed lower levels of GSH in the PDA@DG3@PEG@FA group than in the control group. Markers of oxidative stress indicated changes in the organs of animals receiving PDA nanoparticles with PAMAM dendrimers functionalized with FA in CT-PTT of liver cancer under in vivo conditions. Our work will provide insights into oxidative stress, which can be an indicator of the toxic potential of PDA nanoparticles and provide new strategies to improve existing therapies.

The development of multifunctional drug delivery systems combining two or more nanoparticle-mediated therapies for efficient cancer treatment is highly desired. To face this challenge, a photothermally active polydopamine (PDA) nanoparticle-based platform was designed for the loading of chemotherapeutic drug and targeting of cancer cells. PDA spheres were first functionalized with polyamidoamine (PAMAM) dendrimers followed by the conjugation with polyethylene glycol (PEG) moieties and folic acid (FA) targeting ligand. The anticancer drug doxorubicin (DOX) was then absorbed on the particle surface. We performed the physico-chemical characterization of this versatile material and we assessed further its possible application in chemo- and photothermal therapy using liver cancer cell model. These nanoparticles exhibited high near-infrared photothermal conversion efficacy and allowed for loading of the drug, which upon release in specifically targeted cancer cells suppressed their growth. Using cell proliferation, membrane damage, apoptosis, and oxidative stress assays we demonstrated high performance of this nanosystem in cancer cell death induction, providing a novel promising approach for cancer therapy.

Glioblastoma (GBM) is one of the most aggressive and hard to treat cancers. Traditional anti-cancer treatment methods have low efficiency and the lifespan after diagnosis is only 12–18 months. Brain tumor cells overexpress many proteins that play an important role in tumor progression and can be used as therapeutic targets. One of the promising approaches in cancer treatment is down-regulation of an extracellular matrix glycoprotein – Tenascin-C (TN-C) through RNA interference therapy. However, the effective delivery of double stranded RNA with one strand complementary to TN-C mRNA sequence is difficult due to rapid degradation by nucleases and low intracellular uptake. Polydopamine (PDA), a biomimetic polymer characterized by high biocompatibility and simple modification ability, is commonly used in nanobiomedicine to create a drug/gene delivery vehicle. Furthermore, photothermal characteristics of this polymer enable its application in photothermal therapy (PTT), which is a great option for cancer treatment. Here we synthesize PDA nanoparticles (NPs) coated with polyamidoamine dendrimers generation 3.0 (DD3.0) for therapeutic anti-TN-C RNA and doxorubicin delivery. As prepared PDA@DD3.0 NPs are then used in combined drug delivery, gene silencing, and PTT of GBM. The obtained materials are analyzed in terms of physicochemical and photothermal properties as well as their cytotoxicity, using human GBM cells. The results demonstrate that the obtained nanocarriers are effective non-viral vehicle for combined therapeutic approach for killing glioma cells via anti-TN-C RNA delivery and combined chemo-PTT therapy (CT-PTT). The application of PDA@DD3.0 NPs contributed to the 3-fold reduction in the proliferation rate of GBM cells, a decrease in the level of TN-C expression (by 30%) and a reduction in the number of viable cells by up to 20%.