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Pharmaceutics
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Innovative Drug Delivery Strategies for Targeted Cancer Immunotherapy
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Innovative Drug Delivery Strategies for Targeted Cancer Immunotherapy

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

Deadline for manuscript submissions: 30 September 2026 | Viewed by 9649

Special Issue Editor

Dr. Jingjing Sun

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68105, USA
Interests: prodrug micelles; nanocarrier; biomaterials; cancer immunotherapy

Special Issue Information

Dear Colleagues,

Cancer immunotherapy, including checkpoint inhibitors, adoptive cell transfer, cancer vaccines, and cytokines, has emerged as a revolutionary approach to treating various malignancies by harnessing the body’s immune system. Despite its promise, the clinical success of immunotherapy is often limited by therapeutic agents’ delivery efficiency and specificity. Innovative drug delivery strategies are essential to overcome these barriers, enhancing the delivery and uptake of immunotherapeutic agents and reducing systemic toxicity. By incorporating cutting-edge technologies, researchers are developing various delivery systems (e.g., liposomes, polymeric carriers, inorganic nanoparticles, extracellular vesicles, cell membrane-coated nanoparticles) that can selectively target tumor and immune cells, providing controlled release of therapeutics to modulate the immune response. This Special Issue focuses on the latest advancements in drug delivery systems engineered to enhance the efficacy and specificity of cancer immunotherapies.

We are pleased to invite you to contribute to this Special Issue by submitting original research articles, reviews, and case studies. Your contributions will help advance the field and foster collaboration among researchers and clinicians working towards more effective cancer treatments.

I look forward to receiving your contributions.

Dr. Jingjing Sun
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 250 words) can be sent to the Editorial Office for assessment.

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

  • immunomodulatory agents
  • cancer immunotherapy
  • drug delivery
  • nanoparticles
  • checkpoint inhibitors
  • nanocarriers

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Published Papers (4 papers)

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Research

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24 pages, 24946 KB  
Article
Hybrid Dihydropyrimidinones Targeting AKT Signaling: Antitumor Activity in Hormone-Dependent 2D and 3D Cancer Models
by Amanda Helena Tejada, Samuel José Santos, Gabriel Tofolli Lobo, Abu-Bakr Adetayo Ariwoola, Aryel José Alves Bezerra, Giulia Rodrigues Stringhetta, Izabela Natalia Faria Gomes, Luciane Sussuchi da Silva, Rui Manuel V. Reis, Daniel D’Almeida Preto, Dennis Russowsky and Renato José Silva-Oliveira
Pharmaceutics 2025, 17(11), 1470; https://doi.org/10.3390/pharmaceutics17111470 - 14 Nov 2025
Viewed by 569
Abstract
Background/Objectives: The development of effective oncologic therapies with fewer adverse effects is often limited by the intrinsic and acquired resistance of tumor cells. Hybrid molecules, rationally designed to combine different pharmacophores, represent a promising strategy by providing synergistic effects, dose reduction, and a [...] Read more.
Background/Objectives: The development of effective oncologic therapies with fewer adverse effects is often limited by the intrinsic and acquired resistance of tumor cells. Hybrid molecules, rationally designed to combine different pharmacophores, represent a promising strategy by providing synergistic effects, dose reduction, and a lower risk of resistance. In this study, the antitumor potential and mechanisms of action of 22 novel hybrid compounds derived from xanthene and pyran scaffolds (SJ022–SJ103) were investigated. The hybrids were initially evaluated through in vitro screening in four breast, three ovarian, and two prostate cancer cell lines, followed by the selection of T-47D, OVCAR-3, and LNCaP cells for detailed assays assessing cytotoxicity, apoptosis, cell cycle distribution, DNA damage, caspase-3/7 activity, morphology, and PI3K/AKT/mTOR pathway modulation. Methods: Cytotoxicity assays were performed in the selected cell lines, while mechanistic studies included apoptosis and cell cycle analysis by flow cytometry, γH2AX detection, Western blotting for PI3K/AKT/mTOR pathway proteins, and 3D spheroid assays. Combinatorial effects with hormone therapies (tamoxifen, fulvestrant, and letrozole) and the AKT inhibitor MK2206 were evaluated. AKT silencing by esiRNA and molecular docking was performed to confirm target engagement. Results: SJ028 demonstrated broad activity across all tested cell lines, whereas SJ064 and SJ078 exhibited higher selectivity. Treatments induced apoptosis, S/G2-M arrest, and DNA damage, accompanied by decreased phospho-AKT levels and stable PI3K and mTOR expression. In 3D models, the hybrids increased caspase-3/7 activity and necrotic core expansion. Co-administration with hormone therapies resulted in synergistic effects in breast and ovarian cancer cells, reducing IC50 values by more than 50% in both parental and resistant models, while combinations with MK2206 were antagonistic across all tumor subtypes. AKT silencing abrogated cytotoxicity, and docking confirmed SJ028 binding to AKT. Conclusions: Xanthene- and pyran-based hybrids—particularly SJ028, SJ064, and SJ078—showed strong antitumor activity through apoptosis induction, cell cycle arrest, and PI3K/AKT pathway modulation. Their preserved efficacy in resistant models and synergistic interactions with hormone therapies contrasted with the antagonism observed with AKT inhibition, highlighting their potential as promising candidates for the treatment of hormone-responsive and -resistant cancers. Full article
(This article belongs to the Special Issue Innovative Drug Delivery Strategies for Targeted Cancer Immunotherapy)
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11 pages, 3368 KB  
Article
Synergistic Chemo-Immunotherapy: Recombinant Fusion Protein-Based Surface Modification of NK Cell for Targeted Cancer Treatment
by Su Yeon Lim, Luna Kim, Hongbin Kim, Jeong-Ann Park, Jina Yun and Kwang Suk Lim
Pharmaceutics 2024, 16(9), 1189; https://doi.org/10.3390/pharmaceutics16091189 - 8 Sep 2024
Cited by 5 | Viewed by 2527
Abstract
While traditional combination anticancer treatments have shown promising results, there remains significant interest in developing innovative methods to enhance and integrate chemotherapy and immunotherapy. This study introduces a recombinant fusion protein-based cell surface modification system that synergistically combines chemotherapy and immunotherapy into a [...] Read more.
While traditional combination anticancer treatments have shown promising results, there remains significant interest in developing innovative methods to enhance and integrate chemotherapy and immunotherapy. This study introduces a recombinant fusion protein-based cell surface modification system that synergistically combines chemotherapy and immunotherapy into a single-targeted chemo-immunotherapy approach. A cell surface-modified protein composed of an antibody-specific binding domain and a cell-penetrating domain rapidly converts immune cells into chemo-immuno therapeutics by binding to antibodies on the surface of immune cells. Utilizing a non-invasive, non-toxic approach free of chemical modifications and binding, our system homogeneously transforms immune cells by transiently introducing targeted cytotoxic drugs into them. The surface-engineered immune cells loaded with antibody–drug conjugates (ADCs) significantly inhibit the growth of target tumors and enhance the targeted elimination of cancer cells. Therefore, NK cells modified by the cell surface-modified protein to incorporate ADCs could be expected to achieve the combined effects of targeted cancer cell recognition, chemotherapy, and immunotherapy, thereby enhancing their therapeutic efficacy against cancer. This strategy allows for the efficient and rapid preparation of advanced chemo-immuno therapeutics to treat various types of cancer and provides significant potential to improve the efficacy of cancer treatment. Full article
(This article belongs to the Special Issue Innovative Drug Delivery Strategies for Targeted Cancer Immunotherapy)
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Review

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21 pages, 1300 KB  
Review
Cancer Cell Membrane-Coated NPs as a Biomimetic Strategy for Precision Tumor Therapy
by Junyi Lin, Wei Li, Alaa R. Aboushanab and Jingjing Sun
Pharmaceutics 2025, 17(10), 1322; https://doi.org/10.3390/pharmaceutics17101322 - 11 Oct 2025
Cited by 1 | Viewed by 1943
Abstract
Cancer treatment remains challenging due to the complexity of the tumor microenvironment, which promotes tumor heterogeneity and contributes to the development of multidrug resistance, ultimately hindering drug delivery and reducing therapeutic efficacy. In recent years, biomimetic nanocarriers have emerged as promising tools to [...] Read more.
Cancer treatment remains challenging due to the complexity of the tumor microenvironment, which promotes tumor heterogeneity and contributes to the development of multidrug resistance, ultimately hindering drug delivery and reducing therapeutic efficacy. In recent years, biomimetic nanocarriers have emerged as promising tools to address these challenges. Among them, cancer cell membrane (CCM)-coated nanoparticles (CCM-NPs) have attracted increasing attention due to their unique advantages, including homologous targeting, prolonged circulation mediated by self-recognition, and enhanced tumor penetration. Moreover, CCM-NPs can serve as versatile platforms for tumor vaccines by leveraging their inherent tumor-associated antigens and immunomodulatory potential. By leveraging CCMs to functionalize NPs, researchers have developed innovative approaches to improve drug delivery, enhance tumor immunotherapy, and optimize cancer vaccine efficacy. Despite these advancements, a comprehensive review summarizing the latest progress in CCM-based biomimetic nanocarriers for tumor treatment is lacking. This review integrates recent advances in CCM-NPs for targeted drug delivery and cancer vaccination, and discusses their fabrication, characterization, mechanisms and applications across multiple cancer types, which provides timely insights to guide their future development in precision tumor therapy. Full article
(This article belongs to the Special Issue Innovative Drug Delivery Strategies for Targeted Cancer Immunotherapy)
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33 pages, 8388 KB  
Review
Peptides as Versatile Regulators in Cancer Immunotherapy: Recent Advances, Challenges, and Future Prospects
by Yu Lei, Jiacheng Liu, Yaowei Bai, Chuansheng Zheng and Dongyuan Wang
Pharmaceutics 2025, 17(1), 46; https://doi.org/10.3390/pharmaceutics17010046 - 1 Jan 2025
Cited by 7 | Viewed by 3767
Abstract
The emergence of effective immunotherapies has revolutionized therapies for many types of cancer. However, current immunotherapy has limited efficacy in certain patient populations and displays therapeutic resistance after a period of treatment. To address these challenges, a growing number of immunotherapy drugs have [...] Read more.
The emergence of effective immunotherapies has revolutionized therapies for many types of cancer. However, current immunotherapy has limited efficacy in certain patient populations and displays therapeutic resistance after a period of treatment. To address these challenges, a growing number of immunotherapy drugs have been investigated in clinical and preclinical applications. The diverse functionality of peptides has made them attractive as a therapeutic modality, and the global market for peptide-based therapeutics is witnessing significant growth. Peptides can act as immunotherapeutic agents for the treatment of many malignant cancers. However, a systematic understanding of the interactions between different peptides and the host’s immune system remains unclear. This review describes in detail the roles of peptides in regulating the function of the immune system for cancer immunotherapy. Initially, we systematically elaborate on the relevant mechanisms of cancer immunotherapy. Subsequently, we categorize peptide-based nanomaterials into the following three categories: peptide-based vaccines, anti-cancer peptides, and peptide-based delivery systems. We carefully analyzed the roles of these peptides in overcoming the current barriers in immunotherapy, including multiple strategies to enhance the immunogenicity of peptide vaccines, the synergistic effect of anti-cancer peptides in combination with other immune agents, and peptide assemblies functioning as immune stimulators or vehicles to deliver immune agents. Furthermore, we introduce the current status of peptide-based immunotherapy in clinical applications and discuss the weaknesses and future prospects of peptide-based materials for cancer immunotherapy. Overall, this review aims to enhance comprehension of the potential applications of peptide-based materials in cancer immunotherapy and lay the groundwork for future research and clinical applications. Full article
(This article belongs to the Special Issue Innovative Drug Delivery Strategies for Targeted Cancer Immunotherapy)
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