Cancer Nanopharmaceuticals: Physicochemical Characterization and In Vitro/In Vivo Applications

Zielińska, Aleksandra; Szalata, Marlena; Gorczyński, Adam; Karczewski, Jacek; Eder, Piotr; Severino, Patrícia; Cabeda, José Manuel; Souto, Eliana B.; Słomski, Ryszard

doi:10.3390/cancers13081896

Cited by 20 publications

(14 citation statements)

References 238 publications

(196 reference statements)

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“…Systemic delivery of nano-therapeutics in cancer presents the advantage of improved drug bioavailability and reduced systemic toxicological effects due to highly efficient site targeting ( Zielińska and Szalata, 2021 ). The TME plays a compelling role in cancer development, by providing a complex and dynamic stage for bidirectional interactions between tumor and immune cells in favor of progression and metastasis ( Baghban et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Active Tumor-Targeting Nano-formulations Containing Simvastatin and Doxorubicin Inhibit Melanoma Growth and Angiogenesis

et al. 2022

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Primary melanoma aggressiveness is determined by rapid selection and growth of cellular clones resistant to conventional treatments, resulting in metastasis and recurrence. In addition, a reprogrammed tumor-immune microenvironment supports melanoma progression and response to therapy. There is an urgent need to develop selective and specific drug delivery strategies for modulating the interaction between cancer cells and immune cells within the tumor microenvironment. This study proposes a novel combination therapy consisting of sequential administration of simvastatin incorporated in IL-13-functionalized long-circulating liposomes (IL-13-LCL-SIM) and doxorubicin encapsulated into PEG-coated extracellular vesicles (PEG-EV-DOX) to selectively target both tumor-associated macrophages and melanoma cells. To this end, IL-13 was conjugated to LCL-SIM which was obtained via the lipid film hydration method. EVs enriched from melanoma cells were passively loaded with doxorubicin. The cellular uptake of rhodamine-tagged nano-particles and the antiproliferative potential of the treatments by using the ELISA BrdU-colorimetric immunoassay were investigated in vitro. Subsequently, the therapeutic agents were administered i.v in B16.F10 melanoma-bearing mice, and tumor size was monitored during treatment. The molecular mechanisms of antitumor activity were investigated using angiogenic and inflammatory protein arrays and western blot analysis of invasion (HIF-1) and apoptosis markers (Bcl-xL and Bax). Quantification of oxidative stress marker malondialdehyde (MDA) was determined by HPLC. Immunohistochemical staining of angiogenic markers CD31 and VEGF and of pan-macrophage marker F4/80 was performed to validate our findings. The in vitro data showed that IL-13-functionalized LCL were preferentially taken up by tumor-associated macrophages and indicated that sequential administration of IL-13-LCL-SIM and PEG-EV-DOX had the strongest antiproliferative effect on tumor cells co-cultured with tumor-associated macrophages (TAMs). Accordingly, strong inhibition of tumor growth in the group treated with the sequential combination therapy was reported in vivo. Our data suggested that the antitumor action of the combined treatment was exerted through strong inhibition of several pro-angiogenic factors (VEGF, bFGF, and CD31) and oxidative stress-induced upregulation of pro-apoptotic protein Bax. This novel drug delivery strategy based on combined active targeting of both cancer cells and immune cells was able to induce a potent antitumor effect by disruption of the reciprocal interactions between TAMs and melanoma cells.

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Section: Discussionmentioning

confidence: 99%

Active Tumor-Targeting Nano-formulations Containing Simvastatin and Doxorubicin Inhibit Melanoma Growth and Angiogenesis

et al. 2022

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“…Most effective nanoparticles usually have a mean diameter between 1 and 100 nm, although the size of nanoparticles generally ranges from 1 to 1000 nm, as described by Zielińska et al (2021) [ 61 ]. The solid core of lipid nanoparticles offers several benefits, namely loading of hydrophobic/poorly soluble drugs to improve their solubility in vivo, the protection of loaded drugs against degradation in a physiological environment, and controlled release via a targeted approach.…”

Section: Nanoparticle-related Therapies For Bccmentioning

confidence: 99%

“…The solid core of lipid nanoparticles offers several benefits, namely loading of hydrophobic/poorly soluble drugs to improve their solubility in vivo, the protection of loaded drugs against degradation in a physiological environment, and controlled release via a targeted approach. Nanoparticles can be coated with ligands for site-specific targeting to certain receptors to reduce the risk of systemic distribution of anticancer drugs and thus reduce the toxicity of the treatment [ 61 ].…”

Section: Nanoparticle-related Therapies For Bccmentioning

confidence: 99%

Basal Cell Carcinoma: Pathology, Current Clinical Treatment, and Potential Use of Lipid Nanoparticles

Łasińska

Zielińska

Mackiewicz

et al. 2022

Cancers

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Skin cancer is the most common type of carcinoma diagnosed worldwide, with significant morbidity and mortality rates among Caucasians, in particular basal cell carcinoma (BCC). The main risk factors of BCC are well-identified, and there are many chemotherapeutic drugs available for its treatment. The effectiveness of therapeutic options is governed by several factors, including the location of the tumor, its size, and the presence of metastases (although rare for BCC). However, available treatments are based on non-targeted approaches, which encounter a significant risk of systemic toxicity in several organs. Site-specific chemotherapy for BCC has been proposed via the loading of anticancer drugs into nanoparticles. Among various types of nanoparticles, in this review, we focus on potential new regimens for the treatment of BCC using classical anticancer drugs loaded into novel lipid nanoparticles. To meet patient aesthetic expectations and enhance the effectiveness of basal cell carcinoma treatment, new therapeutic topical strategies are discussed, despite a limited number of reports available in the literature.

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“…The application of nanomedicine in cancer therapy, with the aim of striking and selectively destroying the targets, has aroused significant interest both in the academic and the industrial fields [ 3 , 4 ]. Cancer nanomedicine is a constantly progressing science that is based on innovative physicochemical concepts and materials, and has been exploited to design nanotherapeutics, i.e., submicron novel drug-carrier systems, defined as nanocarriers, that may be able to overcome the many limitations of conventional drugs, such as poor water solubility, unfair oral bioavailability, non-specific biodistribution and a lack of targeting ability [ 5 , 6 , 7 , 8 ]. Nanomedicine has gained considerable interest due to its ability to overcome the challenges of tumor therapy, such as metastasis and multi-drug resistant or recurrent tumors [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Developing Actively Targeted Nanoparticles to Fight Cancer: Focus on Italian Research

et al. 2021

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Active targeting is a valuable and promising approach with which to enhance the therapeutic efficacy of nanodelivery systems, and the development of tumor-targeted nanoparticles has therefore attracted much research attention. In this field, the research carried out in Italian Pharmaceutical Technology academic groups has been focused on the development of actively targeted nanosystems using a multidisciplinary approach. To highlight these efforts, this review reports a thorough description of the last 10 years of Italian research results on the development of actively targeted nanoparticles to direct drugs towards different receptors that are overexpressed on cancer cells or in the tumor microenvironment. In particular, the review discusses polymeric nanocarriers, liposomes, lipoplexes, niosomes, solid lipid nanoparticles, squalene nanoassemblies and nanobubbles. For each nanocarrier, the main ligands, conjugation strategies and target receptors are described. The literature indicates that polymeric nanoparticles and liposomes stand out as key tools for improving specific drug delivery to the site of action. In addition, solid lipid nanoparticles, squalene nanoparticles and nanobubbles have also been successfully proposed. Taken together, these strategies all offer many platforms for the design of nanocarriers that are suitable for future clinical translation.

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Cancer Nanopharmaceuticals: Physicochemical Characterization and In Vitro/In Vivo Applications

Cited by 20 publications

References 238 publications

Active Tumor-Targeting Nano-formulations Containing Simvastatin and Doxorubicin Inhibit Melanoma Growth and Angiogenesis

Active Tumor-Targeting Nano-formulations Containing Simvastatin and Doxorubicin Inhibit Melanoma Growth and Angiogenesis

Basal Cell Carcinoma: Pathology, Current Clinical Treatment, and Potential Use of Lipid Nanoparticles

Developing Actively Targeted Nanoparticles to Fight Cancer: Focus on Italian Research

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