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Pharmaceutics
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Lipid Nanostructures as Drug Carriers for Cancer Therapy
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Lipid Nanostructures as Drug Carriers for Cancer Therapy

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (20 December 2024) | Viewed by 6915

Special Issue Editor

Prof. Dr. Luís Alexandre Muehlmann

E-Mail Website1 Website2
Guest Editor
Faculty of Ceilândia, University of Brasília, Brasília 70910-900, Brazil
Interests: nanotechnology; cancer; nanostructures; biochemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer constitutes a major cause of death worldwide, and the prevailing pharmacotherapies frequently cause debilitating adverse effects. In recent decades, various therapeutic modalities have emerged to address these issues, including immunotherapy, tailored precision chemotherapy, and nanomedicine. Notably, the utilization of nanostructures has demonstrated considerable potential in enhancing both drug biodistribution and their interactions with target cells, thereby offering prospects for improved outcomes in cancer therapy. Among the myriad of nanostructures proposed in the scientific literature, lipid-based formulations have exhibited superior performance and biocompatibility. Furthermore, the diverse range of human-compatible lipids has empowered researchers to fabricate an expansive repertoire of lipid nanostructures endowed with distinctive attributes, such as sustained drug release and prolonged circulation times. This Special Issue is dedicated to elucidating the latest advancements in lipid nanostructures engineered as drug carriers for cancer therapeutics.

Prof. Dr. Luís Alexandre Muehlmann
Guest Editor

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Keywords

  • cancer
  • lipid nanostructures
  • nanomedicine
  • nanotechnology
  • chemotherapy
  • immunotherapy

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Published Papers (4 papers)

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Research

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15 pages, 4925 KiB  
Article
C3-Liposome Delivery of MUC1 Peptide and TLR Agonists Enhances Adaptive Immunity and Results in Sex-Based Tumor Growth Differences
by Shahab Soltani, Ameneh Arabi, Kristine Mann, Austin Hess, Holly A. Martinson and Max Kullberg
Pharmaceutics 2025, 17(4), 468; https://doi.org/10.3390/pharmaceutics17040468 - 3 Apr 2025
Viewed by 386
Abstract
Background: Mucin-1 (MUC1) is a glycoprotein that is hypoglycosylated and overexpressed in most adenocarcinomas, making it a promising target for cancer vaccines. Our group previously demonstrated that C3 (OPSS)-liposomes enhance antigen uptake by antigen-presenting cells (APCs) via the complement C3 pathway and, [...] Read more.
Background: Mucin-1 (MUC1) is a glycoprotein that is hypoglycosylated and overexpressed in most adenocarcinomas, making it a promising target for cancer vaccines. Our group previously demonstrated that C3 (OPSS)-liposomes enhance antigen uptake by antigen-presenting cells (APCs) via the complement C3 pathway and, when combined with toll-like receptor (TLR) agonists, reduce tumor growth in murine cancer models. Methods: In the present study, we evaluate the immunogenicity of MUC1 peptide vaccines encapsulated in C3-liposomes, with and without TLR agonists, using MUC1-tolerant transgenic mice challenged with Lewis lung carcinoma (LLC.MUC1) cells. To assess vaccine effectiveness, tumor volumes were measured, and flow cytometry and ELISA and ELISPOT assays were used to assess the immune response. Results: Both male and female C57BL/6 transgenic mice vaccinated with MUC1 C3-liposomes developed significantly smaller tumors than those vaccinated with free MUC1 peptide or PBS. Notably, a sex-dependent response emerged in mice vaccinated with MUC1 C3-liposomes with TLR agonists (TLR4, TLR7/8, and TLR9); male mice exhibited greater tumor suppression than females. Flow cytometry analysis revealed that female mice had significantly higher levels of CD11b+, LY6C+, and LY6G+ MDSC cells, suggesting a potential mechanism for the sex difference. Additionally, MUC1 C3-liposome vaccination elicited robust adaptive immune responses, including significantly higher levels of IFN-γ-producing T cells and MUC1-specific IgG antibodies compared to non-encapsulated MUC1 or TLR adjuvant-only formulations. Conclusions: These findings underscore the potential of C3-liposome-based antigen vaccines to enhance anti-tumor immunity and highlight the impact of sex differences in vaccine efficacy. Full article
(This article belongs to the Special Issue Lipid Nanostructures as Drug Carriers for Cancer Therapy)
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22 pages, 8044 KiB  
Article
Direct and Abscopal Antitumor Responses Elicited by AlPcNE-Mediated Photodynamic Therapy in a Murine Melanoma Model
by José Athayde Vasconcelos Morais, Pedro H. A. Barros, Marcelo de Macedo Brigido, Clara Luna Marina, Anamelia Bocca, André de Lima e Silva Mariano, Paulo E. N. de Souza, Karen L. R. Paiva, Marina Mesquita Simões, Sonia Nair Bao, Luana C. Camargo, João P. Figueiró Longo, Amanda Alencar Cabral Morais, Ricardo B. de Azevedo, Marcio J. P. Fonseca and Luis A. Muehlmann
Pharmaceutics 2024, 16(9), 1177; https://doi.org/10.3390/pharmaceutics16091177 - 6 Sep 2024
Cited by 2 | Viewed by 1455
Abstract
Melanoma, the most aggressive form of skin cancer, presents a major clinical challenge due to its tendency to metastasize and recalcitrance to traditional therapies. Despite advances in surgery, chemotherapy, and radiotherapy, the outlook for advanced melanoma remains bleak, reinforcing the urgent need for [...] Read more.
Melanoma, the most aggressive form of skin cancer, presents a major clinical challenge due to its tendency to metastasize and recalcitrance to traditional therapies. Despite advances in surgery, chemotherapy, and radiotherapy, the outlook for advanced melanoma remains bleak, reinforcing the urgent need for more effective treatments. Photodynamic therapy (PDT) has emerged as a promising alternative, leading to targeted tumor destruction with minimal harm to surrounding tissues. In this study, the direct and abscopal antitumor effects of PDT in a bilateral murine melanoma model were evaluated. Although only one of the two tumors was treated, effects were observed in both. Our findings revealed significant changes in systemic inflammation and alterations in CD4+ and CD8+ T cell populations in treated groups, as evidenced by blood analyses and flow cytometry. High-throughput RNA sequencing (RNA-Seq) further unveiled shifts in gene expression profiles in both treated and untreated tumors. This research sheds light on the novel antitumor and abscopal effects of nanoemulsion of aluminum chloride phthalocyanine (AlPcNE)-mediated PDT in melanoma, highlighting the potential of different PDT protocols to modulate immune responses and to achieve more effective and targeted cancer treatments. Full article
(This article belongs to the Special Issue Lipid Nanostructures as Drug Carriers for Cancer Therapy)
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Review

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36 pages, 3932 KiB  
Review
Innovations in Cancer Therapy: Endogenous Stimuli-Responsive Liposomes as Advanced Nanocarriers
by Jazmín Torres, Johanna Karina Valenzuela Oses, Antonio María Rabasco-Álvarez, María Luisa González-Rodríguez and Mónica Cristina García
Pharmaceutics 2025, 17(2), 245; https://doi.org/10.3390/pharmaceutics17020245 - 13 Feb 2025
Viewed by 1043
Abstract
Recent advancements in nanotechnology have revolutionized cancer therapy—one of the most pressing global health challenges and a leading cause of death—through the development of liposomes (L), lipid-based nanovesicles known for their biocompatibility and ability to encapsulate both hydrophilic and lipophilic drugs. More recent [...] Read more.
Recent advancements in nanotechnology have revolutionized cancer therapy—one of the most pressing global health challenges and a leading cause of death—through the development of liposomes (L), lipid-based nanovesicles known for their biocompatibility and ability to encapsulate both hydrophilic and lipophilic drugs. More recent innovations have led to the creation of stimuli-responsive L that release their payloads in response to specific endogenous or exogenous triggers. Dual- and multi-responsive L, which react to multiple stimuli, offer even greater precision, improving therapeutic outcomes while reducing systemic toxicity. Additionally, these smart L can adjust their physicochemical properties and morphology to enable site-specific targeting and controlled drug release, enhancing treatment efficacy while minimizing adverse effects. This review explores the latest advancements in endogenous stimuli-responsive liposomal nanocarriers, as well as dual- and multi-responsive L that integrate internal and external triggers, with a focus on their design strategies, mechanisms, and applications in cancer therapy. Full article
(This article belongs to the Special Issue Lipid Nanostructures as Drug Carriers for Cancer Therapy)
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31 pages, 1659 KiB  
Review
Lipid Nanoparticles in Lung Cancer Therapy
by Hossein Omidian, Erma J. Gill and Luigi X. Cubeddu
Pharmaceutics 2024, 16(5), 644; https://doi.org/10.3390/pharmaceutics16050644 - 10 May 2024
Cited by 11 | Viewed by 3219
Abstract
This manuscript explores the use of lipid nanoparticles (LNPs) in addressing the pivotal challenges of lung cancer treatment, including drug delivery inefficacy and multi-drug resistance. LNPs have significantly advanced targeted therapy by improving the precision and reducing the systemic toxicity of chemotherapeutics such [...] Read more.
This manuscript explores the use of lipid nanoparticles (LNPs) in addressing the pivotal challenges of lung cancer treatment, including drug delivery inefficacy and multi-drug resistance. LNPs have significantly advanced targeted therapy by improving the precision and reducing the systemic toxicity of chemotherapeutics such as doxorubicin and paclitaxel. This manuscript details the design and benefits of various LNP systems, including solid lipid–polymer hybrids, which offer controlled release and enhanced drug encapsulation. Despite achievements in reducing tumor size and enhancing survival, challenges such as manufacturing complexity, biocompatibility, and variable clinical outcomes persist. Future directions are aimed at refining targeting capabilities, expanding combinatorial therapies, and integrating advanced manufacturing techniques to tailor treatments to individual patient profiles, thus promising to transform lung cancer therapy through interdisciplinary collaboration and regulatory innovation. Full article
(This article belongs to the Special Issue Lipid Nanostructures as Drug Carriers for Cancer Therapy)
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