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Pharmaceuticals
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Self-Assembling Nanostructures for Cancer Therapy
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Self-Assembling Nanostructures for Cancer Therapy

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmaceutical Technology".

Deadline for manuscript submissions: closed (25 July 2025) | Viewed by 3480

Special Issue Editor

Prof. Dr. André Moreni Lopes

E-Mail Website
Guest Editor
Department of Biotechnology, Lorena School of Engineering, University of São Paulo (DEBIQ, EEL/USP), São Paulo, Brazil
Interests: nanobiotechnology; drug delivery systems (DDS); protein drugs; therapeutic biomolecules; (bio)molecules encapsulation; biomaterials; polymeric micelles; polymeric vesicles (polymersomes); pluronic block copolymers; smart DDS
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Self-Assembling Nanostructures for Cancer Therapy is a Special Issue showcasing innovative research on the use of nanostructures in cancer treatment. We are particularly interested in studies involving drug delivery systems (DDSs) formed by self-assembly in aqueous environments with diverse compositions, such as surfactants, amphiphilic copolymers, and lipids, and in shapes like micelles, vesicles, and cubosomes. Submissions on other types of self-assembling nanostructures are also welcome. Additionally, contributions on stimuli-responsive polymers, dual co-encapsulation, delivery systems, and biopharmaceutical applications in cancer therapy are highly encouraged. Studies on nanostructures incorporated or embedded in 3D scaffolds or hydrogels (e.g., composed of polysaccharides, alginates, chitosan, xanthan, collagen, fibrin, fibrinogen, hyaluronic acid, polyesters, and other biomaterials) are also considered. In addition, we welcome research focusing on different cancer cell types (in vitro studies) and in vivo studies for this Special Issue.

Prof. Dr. André Lopes
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • drug delivery systems
  • polymeric micelles
  • polymeric vesicles (polymersomes)
  • surfactants
  • amphiphilic copolymers
  • stimuli-responsive polymers
  • cancer therapy
  • drugs
  • biopharmaceuticals
  • dual delivery

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Published Papers (3 papers)

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Research

19 pages, 3915 KiB  
Article
Nanostructured Strategies for Melanoma Treatment—Part II: Targeted Topical Delivery of Curcumin via Poloxamer-Based Thermosensitive Hydrogels
by Valentina Paganini, Daniela Monti, Patrizia Chetoni, Susi Burgalassi, Andrea Cesari, Fabio Bellina and Silvia Tampucci
Pharmaceuticals 2025, 18(3), 337; https://doi.org/10.3390/ph18030337 - 27 Feb 2025
Viewed by 726
Abstract
Background/Objectives: Curcumin (CUR) is a natural compound with notable antitumor properties but faces limitations in topical applications due to poor aqueous solubility, instability, and insufficient skin penetration. To overcome these challenges, a nanomicellar formulation (TPGS30ELP15) was developed to enhance CUR solubility, stability, [...] Read more.
Background/Objectives: Curcumin (CUR) is a natural compound with notable antitumor properties but faces limitations in topical applications due to poor aqueous solubility, instability, and insufficient skin penetration. To overcome these challenges, a nanomicellar formulation (TPGS30ELP15) was developed to enhance CUR solubility, stability, and skin penetration. This study aimed at evaluating the skin permeation and retention of CUR when delivered through nanomicelles alone or combined with a thermosensitive hydrogel for potential melanoma therapy. Methods: A CUR-loaded nanomicellar formulation containing CUR 5 mM was developed, characterized by particle sizes of 12–25 nm. Skin permeation studies utilized pig ear skin to assess CUR localization using both HPLC quantitative analysis and confocal microscopy. To improve patient comfort and application efficiency, the nanomicellar dispersion was incorporated into a thermosensitive hydrogel based on 16% Kolliphor® P407 and was able to undergo a sol–gel transition at skin temperature (32–36 °C). Formulations were evaluated for physicochemical properties, stability, and CUR distribution within skin layers using in vitro permeation assays. Results: CUR-loaded nanomicelles demonstrated selective localization in the viable epidermis (100–150 µm depth), bypassing the stratum corneum. The addition of the thermosensitive hydrogel enhanced CUR retention and distribution, prolonging contact at the application site and providing a gradual release profile. The hydrogel’s sol–gel transition properties can facilitate ease of use and patient compliance. The combined system effectively delivered CUR to the basal epidermis, a target site for melanoma treatment, achieving therapeutically relevant drug concentrations. Conclusions: The incorporation of CUR-loaded nanomicelles into a thermosensitive hydrogel enhanced the solubility, stability, and targeted delivery of CUR to skin layers. This dual system represents a promising strategy for improving topical drug delivery for melanoma therapy, addressing limitations associated with CUR’s physicochemical properties while ensuring patient-friendly application and gradual drug release. Full article
(This article belongs to the Special Issue Self-Assembling Nanostructures for Cancer Therapy)
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24 pages, 8116 KiB  
Article
Nanostructured Strategies for Melanoma Treatment—Part I: Design and Optimization of Curcumin-Loaded Micelles for Enhanced Anticancer Activity
by Valentina Paganini, Andrea Cesari, Silvia Tampucci, Patrizia Chetoni, Susi Burgalassi, Michele Lai, Giulia Sciandrone, Silvia Pizzimenti, Fabio Bellina and Daniela Monti
Pharmaceuticals 2025, 18(3), 327; https://doi.org/10.3390/ph18030327 - 26 Feb 2025
Cited by 2 | Viewed by 834
Abstract
Background/Objectives: Melanoma is a pathology that affects a large part of the population, and the currently available therapies have many limitations, including the selective targeting of the site of action. This study explores the development of curcumin (CUR)-loaded nanostructured delivery systems for [...] Read more.
Background/Objectives: Melanoma is a pathology that affects a large part of the population, and the currently available therapies have many limitations, including the selective targeting of the site of action. This study explores the development of curcumin (CUR)-loaded nanostructured delivery systems for topical melanoma treatment, addressing CUR’s limitations in bioavailability, solubility, and stability. Methods: Binary surfactant mixtures of Vitamin E-TPGS (TPGS) and Kolliphor ELP (ELP) were selected to form stable micelles for curcumin encapsulation. A Design of Experiments (DoE) approach was applied to optimize the surfactant ratios for enhanced drug solubilization and improved cytotoxic effects on melanoma cells. The final formulation was characterized using Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Nuclear Magnetic Resonance (NMR) spectroscopy to confirm its properties. Results: The final formulation, TPGS30ELP15, contained 30 mM TPGS and 15 mM ELP and led to formation of nanostructures of the expected size (hydrodinamic diameter, Dh: 13.11 ± 0.01 nm; polydispersivity index, PDI = 0.371 ± 0.05), able to solubilize 5.51 ± 1.09 mM CUR. The formulation was stable for a 120-day period stored at 4 °C and room temperature in the dark. Cytotoxicity testing in A375 melanoma cells demonstrated that curcumin-loaded micelles significantly reduced cell viability compared to free curcumin. Long-term exposure (24 h) revealed that free curcumin caused an 85% reduction in cell viability, while TPGS30ELP15 resulted in a 70% reduction. Additionally, free curcumin induced a 30% increase in cytoplasmic area, indicating necrosis, whereas TPGS30ELP15 decreased the cytoplasmic area by 20%, suggesting apoptosis. Conclusions: This study demonstrates that TPGS30ELP15 nanomicelles enhance curcumin’s anticancer effects while promoting apoptosis and minimizing necrosis, which is associated with lower inflammation and tissue damage. These findings suggest that TPGS30ELP15 offers a more favorable therapeutic profile for melanoma treatment, paving the way for safer and more effective topical therapies. Full article
(This article belongs to the Special Issue Self-Assembling Nanostructures for Cancer Therapy)
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18 pages, 6943 KiB  
Article
Dual Chemotherapeutic Loading in Oxalate Transferrin-Conjugated Polymersomes Incorporated into Chitosan Hydrogels for Site-Specific Targeting of Melanoma Cells
by Mariana de C. Aranha, Luciana M. R. Alencar, Eliana B. Souto, Daniel T. Kamei and André M. Lopes
Pharmaceuticals 2024, 17(9), 1177; https://doi.org/10.3390/ph17091177 - 6 Sep 2024
Cited by 1 | Viewed by 1366
Abstract
In this work, we developed a smart drug delivery system composed of poly (ethylene glycol)-block-poly (ε-caprolactone) (PEG-PCL)-based polymersomes (Ps) loaded with doxorubicin (DOX) and vemurafenib (VEM). To enhance targeted delivery to malignant melanoma cells, these drug-loaded nanovesicles were conjugated to the [...] Read more.
In this work, we developed a smart drug delivery system composed of poly (ethylene glycol)-block-poly (ε-caprolactone) (PEG-PCL)-based polymersomes (Ps) loaded with doxorubicin (DOX) and vemurafenib (VEM). To enhance targeted delivery to malignant melanoma cells, these drug-loaded nanovesicles were conjugated to the oxalate transferrin variant (oxalate Tf) and incorporated into three-dimensional chitosan hydrogels. This innovative approach represents the first application of oxalate Tf for the precision delivery of drug-loaded polymersomes within a semi-solid dosage form based on chitosan hydrogels. These resulting semi-solids exhibited a sustained release profile for both encapsulated drugs. To evaluate their potency, we compared the cytotoxicity of native Tf-Ps with oxalate Tf-Ps. Notably, the oxalate Tf-Ps demonstrated a 3-fold decrease in cell viability against melanoma cells compared to normal cells and were 1.6-fold more potent than native Tf-Ps, indicating the greater potency of this nanoformulation. These findings suggest that dual-drug delivery using an oxalate-Tf-targeting ligand significantly enhances the drug delivery efficiency of Tf-conjugated nanovesicles and offers a promising strategy to overcome the challenge of multidrug resistance in melanoma therapy. Full article
(This article belongs to the Special Issue Self-Assembling Nanostructures for Cancer Therapy)
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