Advanced Nanocarriers for Targeted Drug and Gene Delivery

Topic Information

Dear Colleague,

Advanced nanocarriers represent a cutting-edge method for conducting precision medicine, being capable of targeting and delivering drugs and genetic materials to specific cells or tissues while minimizing off-target effects.  These nanosystems, based on polymeric, lipid or inorganic nanoparticles, include liposomes, polymeric nanoparticles and micelles, dendritic macromolecules, DNA nanostructures and exosomes. Nanocarriers are designed to enhance bioavailability, improve pharmacokinetics and overcome biological barriers, such as the blood–brain barrier or the tumor microenvironment. Therefore, advanced nanocarriers hold great promise for revolutionizing the processes of drug and gene delivery, offering the potential to improve the treatment of a wide range of diseases, including cancer; infectious, neurodegenerative and genetic diseases; and genetic disorders, with the possibility of being used to create personalized treatment strategies. However, challenges in scalability, biocompatibility and long-term safety still exist, driving continuous research on the design and transformation of nanomaterials. Potential topics include, but are not limited to, the following: 

• Nanocarrier Design and Optimization: Tailoring nanocarrier properties (size, shape, surface chemistry) and incorporating targeting ligands (e.g., antibodies, peptides, aptamers) to enhance cellular uptake and specificity.
• Stimuli-Responsive Systems: Facilitating pH-, redox-, or enzyme-triggered release for spatiotemporal control.
• Active and Passive Targeting: Ligand-functionalized carriers for receptor-mediated uptake (e.g., in cancer or inflamed tissues).
• Gene Delivery: Non-viral vectors (e.g., cationic polymers, lipid nanoparticles) for CRISPR, siRNA or mRNA delivery.
• Barrier Penetration: Strategies to cross the blood–brain barrier or tumor stroma.
• Applications of Nanocarriers: Spanning oncology, neurology and regenerative medicine, with an emerging focus on personalized nanomedicine and combination therapies.
• Multifunctional Nanocarriers: Integration of multiple functionalities into nanocarriers to enhance their theranostic capabilities (diagnosis and therapy).
• Translational Challenges: Scalability, biocompatibility and regulatory hurdles for their clinical adoption.

Dr. Rita Cortesi
Dr. Maddalena Sguizzato
Dr. Francesca Ferrara
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Antioxidants antioxidants	6.6	12.4	2012	18.7 Days	CHF 2900	Submit
Applied Nano applnano	-	4.6	2020	15.7 Days	CHF 1000	Submit
Biomolecules biomolecules	4.8	9.2	2011	17.9 Days	CHF 2700	Submit
Cancers cancers	4.4	8.8	2009	19.1 Days	CHF 2900	Submit
Molecules molecules	4.6	8.6	1996	15.1 Days	CHF 2700	Submit
Nanomaterials nanomaterials	4.3	9.2	2010	14 Days	CHF 2400	Submit
Onco onco	-	-	2021	23.7 Days	CHF 1000	Submit
Pharmaceutics pharmaceutics	5.5	10.0	2009	15.7 Days	CHF 2900	Submit

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Published Papers (7 papers)

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All Biomolecules Molecules Nanomaterials Onco Pharmaceutics Cancers Applied Nano Antioxidants

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18 pages, 1743 KB  

Open AccessReview

Stimuli-Responsive Hydrogels: From Swelling–Deswelling Mechanisms to Biomedical Applications

by Meyoung-Kon Kim, Junghan Lee and A-Ram Kang

Nanomaterials 2026, 16(5), 329; https://doi.org/10.3390/nano16050329 - 5 Mar 2026

Viewed by 417

Abstract

Stimuli-responsive hydrogels, also referred to as “smart” hydrogels, have emerged as versatile platforms for a wide range of biological and biomedical applications owing to their tunable physical, chemical, and biocompatible properties. Their adaptability arises from both their ability to undergo reversible swelling–deswelling and [...] Read more.

Stimuli-responsive hydrogels, also referred to as “smart” hydrogels, have emerged as versatile platforms for a wide range of biological and biomedical applications owing to their tunable physical, chemical, and biocompatible properties. Their adaptability arises from both their ability to undergo reversible swelling–deswelling and volume phase transitions in response to specific physicochemical or biological stimuli and the diversity of synthesis strategies that enable precise tailoring of material properties to meet distinct biomedical demands. Recent advances have led to the development of novel hydrogel designs with improved swelling–deswelling behavior, enhanced stimulus sensitivity, and superior biocompatibility, thereby expanding their applicability in complex biological environments. Despite this progress, challenges such as precise control over hydrogel size and relatively slow response kinetics remain critical barriers to broader biomedical and clinical translation. Addressing these limitations requires strategies, including reducing hydrogel particle dimensions to accelerate response rates and engineering heterogeneous or highly porous gel architectures to increase functional surface area. This review provides a comprehensive classification of stimuli-responsive hydrogels based on their physical properties and response mechanisms, and summarizes recent innovations in their design, synthesis, and biomedical applications. Furthermore, it discusses emerging approaches to enhance the clinical applicability of smart hydrogels in controlled drug release, targeted gene delivery, biosensor development, and tissue engineering. Overall, continued optimization of swelling–deswelling characteristics and material design will be essential to fully realize the potential of stimuli-responsive hydrogels in precision medicine and advanced therapeutic applications. Full article

(This article belongs to the Topic Advanced Nanocarriers for Targeted Drug and Gene Delivery)

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41 pages, 5017 KB  

Open AccessReview

From PEGylation to Next-Generation Polymers: Overcoming Biological Barriers—A Review

by Rizvangul Iminova, Gulzat Berganayeva, Aliya Zhurtbayeva, Lazzat Abdurakhmanova, Almagul Almabekova, Daniil Shepilov, Gulzira Vassilina, Akmaral Nurmahanova, Gulfairuz Kairalapova and Moldyr Dyusebaeva

Molecules 2026, 31(4), 675; https://doi.org/10.3390/molecules31040675 - 15 Feb 2026

Viewed by 493

Abstract

Poly(ethylene glycol) (PEG) has long stood as the prevailing standard in drug delivery, celebrated for its capacity to enhance solubility, extend circulation, and improve pharmacological performance. Nevertheless, the emergence of anti-PEG antibodies, accelerated clearance, and limited biodegradability increasingly undermine its role as a [...] Read more.

Poly(ethylene glycol) (PEG) has long stood as the prevailing standard in drug delivery, celebrated for its capacity to enhance solubility, extend circulation, and improve pharmacological performance. Nevertheless, the emergence of anti-PEG antibodies, accelerated clearance, and limited biodegradability increasingly undermine its role as a universal solution. In response, a new generation of polymers has been developed to address these shortcomings, offering the potential to sustain or surpass PEG’s benefits while mitigating immunogenicity, improving biocompatibility, and enabling finer control over therapeutic fate. This review examines current research to articulate a coherent perspective on the replacement of PEG, tracing how advances in polymer design are reshaping the foundations of targeted drug delivery. Taken together, these developments signal not only a corrective to the limitations of PEG but also a broader paradigm shift toward safer, more versatile, and clinically translatable systems that define the next frontier in precision therapeutics. Full article

(This article belongs to the Topic Advanced Nanocarriers for Targeted Drug and Gene Delivery)

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13 pages, 3685 KB  

Open AccessArticle

Boron Theranostic Nanoplatform Utilizing a GO@Carborane@Au Hybrid Framework for Targeted Delivery

by Václav Ranc and Ludmila Žárská

Pharmaceutics 2026, 18(2), 188; https://doi.org/10.3390/pharmaceutics18020188 - 31 Jan 2026

Viewed by 537

Abstract

Background: Boron neutron capture therapy (BNCT) represents a highly selective therapeutic modality for recalcitrant cancers, leveraging the nuclear reaction initiated by thermal neutron capture in boron-10 (¹⁰B) to deliver high-linear energy transfer radiation (α-particles and ⁷Li ions) directly within tumor [...] Read more.

Background: Boron neutron capture therapy (BNCT) represents a highly selective therapeutic modality for recalcitrant cancers, leveraging the nuclear reaction initiated by thermal neutron capture in boron-10 (¹⁰B) to deliver high-linear energy transfer radiation (α-particles and ⁷Li ions) directly within tumor cell boundaries. However, the widespread clinical adoption of BNCT is critically hampered by the pharmacological challenge of achieving sufficiently high, tumor-selective intracellular ¹⁰B concentrations (20–50 μg of ¹⁰B/g tissue). Conventional small-molecule boron carriers often exhibit dose-limiting non-specificity, rapid systemic clearance, and poor cellular uptake kinetics. Methods: To overcome these delivery barriers, we synthesized and characterized a novel dual-modality nanoplatform based on highly biocompatible, functionalized graphene oxide (GO). This platform was structurally optimized via covalent conjugation with high-boron content carborane clusters (dodecacarborane derivatives) for enhanced BNCT efficacy. Crucially, the nanocarrier was further decorated with plasmonic gold nanostructures (AuNPs), endowing the system with intrinsic surface-enhanced Raman scattering (SERS) properties, enabling real-time, high-resolution intracellular tracking and quantification. Results: We evaluated the synthesized GO@Carborane@Au nanoplatforms for their stability, cytotoxicity, and internalization characteristics. Cytotoxicity assays demonstrated excellent biocompatibility against the non-malignant human keratinocyte line (HaCaT) while showing selective toxicity (upon irradiation, if tested) and high cellular uptake efficiency in the aggressive human glioblastoma tumor cell line (T98G). The integrated plasmonic component allowed for the successful, non-destructive monitoring of nanoplatform delivery and accumulation within both HaCaT and T98G cells using SERS microscopy, confirming the potential for pharmacokinetic and biodistribution studies in vivo. Conclusions: This work details the successful synthesis and preliminary in vitro validation of a unique graphene oxide-based dual-modality nanoplatform designed to address the critical delivery and monitoring challenges of BNCT. By combining highly efficient carborane delivery with an integrated photonic trace marker, this system establishes a robust paradigm for next-generation theranostic agents, significantly advancing the potential for precision, image-guided BNCT for difficult-to-treat cancers like glioblastoma. Full article

(This article belongs to the Topic Advanced Nanocarriers for Targeted Drug and Gene Delivery)

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21 pages, 5367 KB  

Open AccessArticle

Fluorescent Nanoporous Gene Drugs with Fenton-like Catalysis Vector Research

by Yulin Li, Jianjun Pan, Lili Xu, Yan Sun and Tong Li

Nanomaterials 2026, 16(2), 120; https://doi.org/10.3390/nano16020120 - 16 Jan 2026

Viewed by 409

Abstract

A multifunctional diagnosis and treatment carrier, ZIF-8@CDs, based on carbon quantum dots (CDs) and the zeolitic imidazolate framework-8 (ZIF-8) metal–organic framework which serves as a core structure for constructing the responsive delivery platform, is developed in this paper. The anticancer drug doxorubicin (DOX) [...] Read more.

A multifunctional diagnosis and treatment carrier, ZIF-8@CDs, based on carbon quantum dots (CDs) and the zeolitic imidazolate framework-8 (ZIF-8) metal–organic framework which serves as a core structure for constructing the responsive delivery platform, is developed in this paper. The anticancer drug doxorubicin (DOX) and Survivin oligo (siRNA) are loaded to form a ZIF-8@CDs/DOX@siRNA dual loading platform. CDs of 5–10 nm are synthesized by the solvent method and combined with ZIF-8. Electron microscopy shows that the composites are nearly spherical particles of approximately 200 nm, and the surface potential decreases from +36 mV before loading CDs to +25.7 mV after loading. The composite system shows unique advantages: (1) It has Fenton-like catalytic activity, catalyzes H₂O₂ to generate hydroxyl radicals, and consumes glutathione in the tumor microenvironment. The level of reactive oxygen species (ROS) in the ZIF-8@CDs group is significantly higher than that in the control group. (2) To achieve visual diagnosis and treatment, its fluorescence intensity is superior to that of the traditional Fluorescein isothiocyanate (FITC)-labeled vector; (3) It has a high loading capacity, with the loading amount of small nucleic acids reaching 36.25 μg/mg, and the uptake rate of siRNA by liver cancer cells is relatively ideal. The ZIF-8@CDs/DOX@siRNA dual-loading system is further constructed. Flow cytometry shows that the apoptosis rate of HepG2 cells induced by the ZIF-8@CDs/DOX@siRNA dual-loading system is 49%, which is significantly higher than that of the single-loading system (ZIF-8@CDs/DOX: 34.3%, ZIF-8@CDs@siRNA: 24.2%) and the blank vector (ZIF-8@CDs: 12.6%). The platform provides a new strategy for the integration of tumor diagnosis and treatment through the multi-mechanism synergy of chemical kinetic therapy, gene silencing and chemotherapy. Full article

(This article belongs to the Topic Advanced Nanocarriers for Targeted Drug and Gene Delivery)

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14 pages, 1406 KB  

Open AccessArticle

DOTAP-Based Hybrid Nanostructured Lipid Carriers for CRISPR–Cas9 RNP Delivery Targeting TGFB1 in Diabetic Nephropathy

by Nurul Jummah, Hanifa Syifa Kamila, Satrialdi, Aluicia Anita Artarini, Ebrahim Sadaqa, Anindyajati and Diky Mudhakir

Pharmaceutics 2026, 18(1), 94; https://doi.org/10.3390/pharmaceutics18010094 - 11 Jan 2026

Viewed by 641

Abstract

Background: Diabetic nephropathy (DN) is largely driven by transforming growth factor-β1 (TGF-β1)-mediated fibrosis. Clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) ribonucleoprotein (RNP) complexes offer precise gene disruption, yet effective non-viral delivery remains a challenge. This study developed cationic lipid-based [...] Read more.

Background: Diabetic nephropathy (DN) is largely driven by transforming growth factor-β1 (TGF-β1)-mediated fibrosis. Clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) ribonucleoprotein (RNP) complexes offer precise gene disruption, yet effective non-viral delivery remains a challenge. This study developed cationic lipid-based hybrid nanostructured lipid carriers (NLCs) for intracellular delivery of TGFB1-targeting RNP as an early-stage platform for DN gene modulation. Methods: A single-guide RNA (sgRNA) targeting human TGFB1 was assembled with Cas9 protein (1:1 and 1:2 molar ratios). Hybrid NLCs comprising squalene, glyceryl trimyristate, and the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) were formulated via optimized emulsification–sonication to achieve sub-100 nm particles. Physicochemical properties, including polydispersity index (PDI), were assessed via dynamic light scattering (DLS), while silencing efficacy in HEK293T cells was quantified using quantitative reverse transcription PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Results: Optimized NLCs achieved hydrodynamic diameters of 65–99 nm (PDI < 0.5) with successful RNP complexation. The 1:2 Cas9:sgRNA formulation produced the strongest gene-editing response, reducing TGFB1 mRNA by 67% (p < 0.01) compared with 39% for the 1:1 ratio. This translated to a significant reduction in TGF-β1 protein (p < 0.05) within 24 h. Conclusions: DOTAP-based hybrid NLCs enable efficient delivery of CRISPR–Cas9 RNP and achieve significant suppression of TGFB1 expression at both transcriptional and protein levels. These findings establish a promising non-viral platform for upstream modulation of profibrotic signaling in DN and support further evaluation in kidney-derived cells and in vivo renal models. Full article

(This article belongs to the Topic Advanced Nanocarriers for Targeted Drug and Gene Delivery)

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19 pages, 4111 KB  

Open AccessArticle

Non-Crosslinked Hyaluronic Acid Redensity 1^® Supports Cell Viability, Proliferation, and Collagen Deposition in Early Burn Management

by Zhifeng Liao, Xi Chen, Romain Brusini, Jimmy Faivre, Lee Ann Applegate, Killian Flegeau and Nathalie Hirt-Burri

Pharmaceutics 2026, 18(1), 21; https://doi.org/10.3390/pharmaceutics18010021 - 23 Dec 2025

Viewed by 1124

Abstract

Background/Objectives: Burn injuries pose a significant challenge due to tissue damage and impaired healing. Cell-based therapies offer promise by delivering therapeutic cells to the wound site. However, effective cell delivery remains a critical hurdle. This study investigates the potential of non-crosslinked hyaluronic acid [...] Read more.

Background/Objectives: Burn injuries pose a significant challenge due to tissue damage and impaired healing. Cell-based therapies offer promise by delivering therapeutic cells to the wound site. However, effective cell delivery remains a critical hurdle. This study investigates the potential of non-crosslinked hyaluronic acid (HA) as a simple, versatile carrier for delivering autologous keratinocytes and fibroblasts to treat early burn wounds. Methods: Primary keratinocytes and fibroblasts were isolated from uninjured adult skin. In addition, fibroblasts and adipose stem cells (ASC) from polydactyly and progenitor fibroblasts were used. Non-cross-linked HA Redensity 1^® (RD1) solutions of varying concentrations were prepared and applied to various in vitro models. Cell viability, proliferation, migration, and collagen stimulation were assessed using standard assays. Additionally, cells were suspended in Redensity 1 and applied to an in vitro de-epidemalized dermis (DED) wound model to examine cell delivery and tissue reformation. Results: Preliminary data demonstrated the feasibility of using non-cross-linked HA RD1 gel as a cell carrier. RD1 gel enhanced cell viability, retention, migration, and collagen deposition. Histological analysis revealed improved cell adhesion and migration. Conclusions: This study provides valuable insight into the potential of non-cross-linked HA RD1 as a simple and effective delivery vehicle for cell therapies in early burn care. Successful translation of this approach could significantly improve clinical outcomes for burn patients. Full article

(This article belongs to the Topic Advanced Nanocarriers for Targeted Drug and Gene Delivery)

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18 pages, 2321 KB  

Open AccessArticle

De Novo Design of High-Affinity HER2-Targeting Protein Minibinders

by Yize Zhao, Wenping Wei, Zijun Cheng, Min Yang and Yunjun Yan

Biomolecules 2025, 15(11), 1587; https://doi.org/10.3390/biom15111587 - 12 Nov 2025

Cited by 1 | Viewed by 2235

Abstract

Human Epidermal Growth Factor Receptor 2 (HER2) is a key therapeutic target in breast cancer. However, the application of existing anti-HER2 antibody drugs is limited by such issues as large molecular weight and poor stability. In this study, a series of small protein [...] Read more.

Human Epidermal Growth Factor Receptor 2 (HER2) is a key therapeutic target in breast cancer. However, the application of existing anti-HER2 antibody drugs is limited by such issues as large molecular weight and poor stability. In this study, a series of small protein minibinders targeting HER2 domain IV were de novo designed using the RFdiffusion method. Candidate molecules were selected through a combination of ProteinMPNN and AlphaFold2 screening, and their binding capabilities were further evaluated using Escherichia coli surface display coupled with flow cytometry analysis. By integrating molecular dynamics simulations, confocal fluorescence imaging, and isothermal titration calorimetry (ITC) experiments, a highly efficient minibinder (0_703_6) with nanomolar affinity and a smaller molecular size was finally identified. Compared with the existing drug molecules, the identified minibinder exhibited approximately threefold higher affinity and a threefold reduction in molecular size. This study provides strong support for the development of novel, stable, and easily expressible HER2-targeted therapeutic molecules and also offers new insights into the rapid development of robust breast cancer drugs that may serve as ideal alternatives to monoclonal antibodies. Full article

(This article belongs to the Topic Advanced Nanocarriers for Targeted Drug and Gene Delivery)

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