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Pharmaceutics
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Nanosystems and Antibody/Peptide Modified Drugs for Cancer Treatment
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Nanosystems and Antibody/Peptide Modified Drugs for Cancer Treatment

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: 30 April 2025 | Viewed by 3121

Special Issue Editors

Prof. Dr. Juan Manuel López Romero

E-Mail Website
Guest Editor
Department of Organic Chemistry, Faculty of Sciences, University of Málaga, 29071 Málaga, Spain
Interests: natural products; alkaloids; terpenes; plant extracts; synthesis of organic compounds; chemical modification of drugs; organic materials: synthesis and nanostructuration of surfaces; nanoparticles for drug delivery; polymers and applications
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Francisco Sarabia

E-Mail Website
Guest Editor
Department of Organic Chemistry, Faculty of Science, University of Málaga, 29071 Málaga, Spain
Interests: natural products; bioactive compounds; total synthesis; antitumor; antibiotics; cyclodepsipeptides; cyclopeptides
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Currently, the first line of treatment in cancers is the surgical removal of solid tumors. After primary surgical resection, the main action includes the intravenous administration of systemic chemotherapy treatments using cytotoxic molecules. However, after that, an important drawback is tumor recurrences caused by cancer cells that evade primary treatment and are incorporated into the blood stream, causing a high number of deaths due to metastasis. Furthermore, current chemotherapy treatments reach toxic levels that damage healthy cells, causing serious side effects such as infection, bleeding and anemia, peripheral neuropathy (pain), allergic reactions, mucositis, and diarrhea, among others, represent a serious limitation and lead to therapy failure. In addition, a specific applied chemotherapeutic treatment may be ineffective due to multidrug resistance (MDR), caused by the resistance of some remaining cancer cells due to the lack of a specific targeting. Finally, their systemic and (therefore not localized) administration represents a great disadvantage since these molecules cannot be administered in low doses and/or gradually. Consequently, it is necessary to discover and develop new chemical formulations capable of improving their antitumor efficiencies in terms of activity and selectivity, compared with conventional chemotherapeutic drugs, currently approved for cancer therapy.

In this context, it is necessary to develop new systems and cytotoxics that increase direct activity on tumor cells and reduce the drug concentration to which the patient is exposed to avoid secondary effects. The Topic presented here aims to solve specific problems associated with cancer recurrence through the development of new antibody/peptide derivatives and analogues with higher antitumor activity, low unwanted secondary effects and better viability compared with the current chemotherapeutic drugs.

Prof. Dr. Juan Manuel López Romero
Prof. Dr. Francisco Sarabia
Guest Editors

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. Pharmaceutics 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

  • antibody
  • peptide
  • vectorized drugs
  • nanocarriers
  • engineered drugs
  • improved drug delivery

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Published Papers (2 papers)

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20 pages, 4296 KiB  
Article
Novel Anti-Trop2 Nanobodies Disrupt Receptor Dimerization and Inhibit Tumor Cell Growth
by Junwen Deng, Zhongmin Geng, Linli Luan, Dingwen Jiang, Jian Lu, Hanzhong Zhang, Bingguan Chen, Xinlin Liu and Dongming Xing
Pharmaceutics 2024, 16(10), 1255; https://doi.org/10.3390/pharmaceutics16101255 - 27 Sep 2024
Viewed by 995
Abstract
Background: Trop2 (trophoblast cell-surface antigen 2) is overexpressed in multiple malignancies and is closely associated with poor prognosis, thus positioning it as a promising target for pan-cancer therapies. Despite the approval of Trop2-targeted antibody–drug conjugates (ADCs), challenges such as side effects, drug resistance, [...] Read more.
Background: Trop2 (trophoblast cell-surface antigen 2) is overexpressed in multiple malignancies and is closely associated with poor prognosis, thus positioning it as a promising target for pan-cancer therapies. Despite the approval of Trop2-targeted antibody–drug conjugates (ADCs), challenges such as side effects, drug resistance, and limited efficacy persist. Recent studies have shown that the dimeric forms of Trop2 are crucial for its oncogenic functions, and the binding epitopes of existing Trop2-targeted drugs lie distant from the dimerization interface, potentially limiting their antitumor efficacy. Method: A well-established synthetic nanobody library was screened against Trop2-ECD. The identified nanobodies were extensively characterized, including their binding specificity and affinity, as well as their bioactivities in antigen-antibody endocytosis, cell proliferation, and the inhibition of Trop2 dimer assembly. Finally, ELISA based epitope analysis and AlphaFold 3 were employed to elucidate the binding modes of the nanobodies. Results: We identified two nanobodies, N14 and N152, which demonstrated high affinity and specificity for Trop2. Cell-based assays confirmed that N14 and N152 can facilitate receptor internalization and inhibit growth in Trop2-positive tumor cells. Epitope analysis uncovered that N14 and N152 are capable of binding with all three subdomains of Trop2-ECD and effectively disrupt Trop2 dimerization. Predictive modeling suggests that N14 and N152 likely target the epitopes at the interface of Trop2 cis-dimerization. The binding modality and mechanism of action demonstrated by N14 and N152 are unique among Trop2-targeted antibodies. Conclusions: we identified two novel nanobodies, N14 and N152, that specifically bind to Trop2. Importantly, these nanobodies exhibit significant anti-tumor efficacy and distinctive binding patterns, underscoring their potential as innovative Trop2-targeted therapeutics. Full article
(This article belongs to the Special Issue Nanosystems and Antibody/Peptide Modified Drugs for Cancer Treatment)
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20 pages, 7246 KiB  
Article
In Vitro/In Vivo Preparation and Evaluation of cRGDyK Peptide-Modified Polydopamine-Bridged Paclitaxel-Loaded Nanoparticles
by Dan Yun, Dengyuan Liu, Jinlin Liu, Yanyi Feng, Hongyu Chen, Simiao Chen and Qingchun Xie
Pharmaceutics 2023, 15(11), 2644; https://doi.org/10.3390/pharmaceutics15112644 - 20 Nov 2023
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Abstract
Cancer remains a disease with one of the highest mortality rates worldwide. The poor water solubility and tissue selectivity of commonly used chemotherapeutic agents contribute to their poor efficacy and serious adverse effects. This study proposes an alternative to the traditional physicochemically combined [...] Read more.
Cancer remains a disease with one of the highest mortality rates worldwide. The poor water solubility and tissue selectivity of commonly used chemotherapeutic agents contribute to their poor efficacy and serious adverse effects. This study proposes an alternative to the traditional physicochemically combined modifications used to develop targeted drug delivery systems, involving a simpler surface modification strategy. cRGDyK peptide (RGD)-modified PLGA nanoparticles (NPs) loaded with paclitaxel were constructed by coating the NP surfaces with polydopamine (PD). The average particle size of the produced NPs was 137.6 ± 2.9 nm, with an encapsulation rate of over 80%. In vitro release tests showed that the NPs had pH-responsive drug release properties. Cellular uptake experiments showed that the uptake of modified NPs by tumor cells was significantly better than that of unmodified NPs. A tumor cytotoxicity assay demonstrated that the modified NPs had a lower IC50 and greater cytotoxicity than those of unmodified NPs and commercially available paclitaxel formulations. An in vitro cytotoxicity study indicated good biosafety. A tumor model in female BALB/c rats was established using murine-derived breast cancer 4T1 cells. RGD-modified NPs had the highest tumor-weight suppression rate, which was higher than that of the commercially available formulation. PTX-PD-RGD-NPs can overcome the limitations of antitumor drugs, reduce drug toxicity, and increase efficacy, showing promising potential in cancer therapy. Full article
(This article belongs to the Special Issue Nanosystems and Antibody/Peptide Modified Drugs for Cancer Treatment)
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