Nano-formulations in disease therapy: designs, advances, challenges, and future directions

Abstract

Nano-formulations, as an innovative drug delivery system, offer distinct advantages in enhancing drug administration methods, improving bioavailability, promoting biodegradability, and enabling targeted delivery. By exploiting the unique size advantages of nano-formulations, therapeutic agents, including drugs, genes, and proteins, can be precisely reorganized at the microscale level. This modification not only facilitates the precise release of these agents but also significantly enhances their efficacy while minimizing adverse effects, thereby creating novel opportunities for treatment of a wide range of diseases. In this review, we discuss recent advancements, challenges, and future perspectives in nano-formulations for therapeutic applications. For this aim, we firstly introduce the development, design, synthesis, and action mechanisms of nano-formulations. Then, we summarize their applications in disease diagnosis and treatment, especially in fields of oncology, pulmonology, cardiology, endocrinology, dermatology, and ophthalmology. Furthermore, we address the challenges associated with the medical applications of nanomaterials, and provide an outlook on future directions based on these considerations. This review offers a comprehensive examination of the current applications and potential significance of nano-formulations in disease diagnosis and treatment, thereby contributing to the advancement of modern medical therapies.

Keywords: Design strategies; Disease therapy; Hybrid nanoparticle; Nano-formulations.

Fig. 1

The historical development of nano-formulations (self-made image by authors)

Fig. 2

The application of nano-formulations in treating diverse diseases (self-made image by authors). A Design and synthesis. Synthesized nano-formulations can be categorized into four main types: liposomes, inorganic NP, polymer-based NP, and hybrid NP. B Action mechanisms. Action mechanisms of NPs primarily including cellular internalization, cytosolic delivery achieved through endosomal escape, and direct intracellular. C Molecular imaging. Nano-formulations play a pivotal role in disease diagnosis, encompassing modalities such as fluorescence imaging (FI), magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET). D Therapeutic applications. Nano-formulations find extensive applications in disease treatment across various medical specialties, including oncology, pulmonology, cardiology, endocrinology, dermatology, and ophthalmology

Fig. 3

Different classes of nano-formulations. A liposomes: including ligand NP, ionic NP, responsive NP (containing magnetic NP, temperature NP, light NP, and pH NP), and long cycle NP; B inorganic nano-formulations: including silica NP, iron oxide NP, gold NP, and Quantum dot; C polymer nano-formulations: including polymer NP, polymersome NP, dendrimer, and polymer micelle; D hybrid nano-formulations: including lipid-polymer NP, lipid-inorganic NP, silica-polymer NP, and protein-drug NP

Fig. 4

Major NP-based delivery methods: A cellular internalization, B cytosolic delivery through endosomal escape, and C direct intracellular delivery

Fig. 5

Schematic model of nano-formulations and cancer diagnosis techniques. A Preparation process of indocyanine green (ICG)-loaded and cancer cell membrane-coated nanoparticles (ICNPs). B Schematic diagram illustrating isotope-targeted ICNPs utilized for dual-modal imaging-guided photothermal therapy. C Synthetic design of F/A-PLGA@DOX/SPIO nanoparticles and schematic representation of their application in tumor MRI Adapted from Chen Z, Zhao P, Luo Z, et al. Cancer Cell Membrane-Biomimetic Nanoparticles for Homologous-Targeting Dual-Modal Imaging and Photothermal Therapy. ACS Nano. 2016;10(11):10,049–57. Gao P, Mei C, He L, et al. Designing multifunctional cancer-targeted nanosystem for magnetic resonance molecular imaging-guided theranostics of lung cancer. Drug Deliv. 2018;25(1):1811–25.

Fig. 6

Schematic model of nano-formulations and cancer metastasis

Fig. 7

Nano-formulations and cancer treatment methods

Fig. 8

Nano-formulations in chemotherapy

Fig. 9

Nano-formulations in immunotherapy

Fig. 10

Schematic model of nano-formulations in gene therapy. A Design and schematic representation of pH-sensitive PEG(HZ)-ECO/siRNA dual nanoparticles. B Assembly schematic of PBA–BADP/mRNA nanoparticles for mRNA delivery and genome editing Adapted from Gujrati M, Vaidya AM, Mack M, et al. Targeted Dual pH-Sensitive Lipid ECO/siRNA Self-Assembly Nanoparticles Facilitate In Vivo Cytosolic sieIF4E Delivery and Overcome Paclitaxel Resistance in Breast Cancer Therapy. Adv Healthc Mater. 2016;5(22):2882–95. Tang Q, Liu J, Jiang Y, et al. Cell-Selective Messenger RNA Delivery and CRISPR/Cas9 Genome Editing by Modulating the Interface of Phenylboronic Acid-Derived Lipid Nanoparticles and Cellular Surface Sialic Acid. ACS Appl Mater Interfaces. 2019;11(50):46585-90

Fig. 11

Mechanisms of nano-formulations and drug resistance

Fig. 12

Schematic model of nano-formulations and multidrug resistance. A The triple-payload delivery platform (HA-HNRplex) adopts a "kill three birds with one stone" strategy, enabling synchronous delivery of PTX, DSF, and Cyt C for the treatment of multidrug-resistant cancers. B Monoclonal antibody MDR1-modified chitosan nanoparticles (CNPs) can overcome acquired resistance to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) across various antitumor targets. C Chemical structure, transformation behavior, and schematic representation of a lysosomal pH-responsive small-molecule-based nanotransformer designed to overcome autophagy-induced drug resistance in cancer Adapted from Zou J, Xing X, Teng C, et al. Cocrystal@protein-anchoring nanococktail for combinatorially treating multidrug-resistant cancer. Acta Pharm Sin B. 2024;14(10):4509–25. Zheng Y, Su C, Zhao L, et al. mAb MDR1-modified chitosan nanoparticles overcome acquired EGFR-TKI resistance through two potential therapeutic targets modulation of MDR1 and autophagy. J Nanobiotechnology. 2017;15(1):66. Ma Z, Lin K, Tang M, et al. A pH-Driven Small-Molecule Nanotransformer Hijacks Lysosomes and Overcomes Autophagy-Induced Resistance in Cancer. Angew Chem Int Ed Engl. 2022;61(35):e202204567

Fig. 13

Nano-formulations for treating pulmonary diseases

Fig. 14

Nano-formulations for molecular imaging

Fig. 15

Nano-formulations for the therapy of AS

Fig. 16

Nano-formulations for the therapy of MI

Fig. 17

Nano-formulations in the therapy for cardiovascular diseases

Fig. 18

Schematic model of nano-formulations in treating diabetes. A Schematic illustration of the action of insulin-loaded and H₂O₂-responsive mesoporous silica nanoparticles (MSNs). B Schematic illustration of the action of Amentoflavone-loaded P (NVP-MGAM)/AF oral microspheres Adapted from Xu B, Jiang G, Yu W, et al. H₂O₂-Responsive mesoporous silica nanoparticles integrated with microneedle patches for the glucose-monitored transdermal delivery of insulin. J Mater Chem B. 2017;5(41):8200–8. Zhang J, Zhou J, Zhang T, et al. Facile Fabrication of an Amentoflavone-Loaded Micelle System for Oral Delivery To Improve Bioavailability and Hypoglycemic Effects in KKAy Mice. ACS Applied Materials & Interfaces. 2019;11(13):12,904–13

Fig. 19

Nano-formulations in treating skin disease

Fig. 20

Nano-formulations in treating ocular diseases