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Review
. 2023 Jan 11;5(3):571-595.
doi: 10.1039/d2na00483f. eCollection 2023 Jan 31.

Nanotechnology-based diagnostics and therapeutics in acute lymphoblastic leukemia: a systematic review of preclinical studies

Affiliations
Review

Nanotechnology-based diagnostics and therapeutics in acute lymphoblastic leukemia: a systematic review of preclinical studies

Reyhane Khademi et al. Nanoscale Adv. .

Abstract

Background: Leukemia is a malignant disease that threatens human health and life. Nano-delivery systems improve drug solubility, bioavailability, and blood circulation time, and release drugs selectively at desired sites using targeting or sensing strategies. As drug carriers, they could improve therapeutic outcomes while reducing systemic toxicity. They have also shown promise in improving leukemia detection and diagnosis. The study aimed to assess the potential of nanotechnology-based diagnostics and therapeutics in preclinical human acute lymphoblastic leukemia (h-ALL). Methods: We performed a systematic search through April 2022. Articles written in English reporting the toxicity, efficacy, and safety of nanotechnology-based drugs (in the aspect of treatment) and specificity, limit of detection (LOD), or sensitivity (in the aspect of the detection field) in preclinical h-ALL were included. The study was performed according to PRISMA instructions. The methodological quality was assessed using the QualSyst tool. Results: A total of 63 original articles evaluating nanotechnology-based therapeutics and 35 original studies evaluating nanotechnology-based diagnostics were included in this review. As therapeutics in ALL, nanomaterials offer controlled release, targeting or sensing ligands, targeted gene therapy, photodynamic therapy and photothermic therapy, and reversal of multidrug-resistant ALL. A narrative synthesis of studies revealed that nanoparticles improve the ratio of efficacy to the toxicity of anti-leukemic drugs. They have also been developed as a vehicle for biomolecules (such as antibodies) that can help detect and monitor leukemic biomarkers. Therefore, nanomaterials can help with early diagnostics and personalized treatment of ALL. Conclusion: This review discussed nanotechnology-based preclinical strategies to achieve ALL diagnosis and therapy advancement. This involves modern drug delivery apparatuses and detection devices for prompt and targeted disease diagnostics. Nonetheless, we are yet in the experimental phase and investigational stage in the field of nanomedicine, with many features remained to be discovered as well as numerous problems to be solved.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1. PRISMA flow diagram of study selection.
Fig. 2
Fig. 2. Control release: drug content liberation from nanocarriers can be stimulated by certain microenvironmental parameters at the target location (e.g., pH change and enzymatic activities) or by external stimuli (e.g., heat, light, electric and magnetic field or ultrasound). Targeting: targeting ligands can specifically attach to the malignant cell (e.g., monoclonal antibodies (mAbs) or sgc8 aptamer). Targeted gene therapy: nanoparticle formation of targeted gene therapy agents (e.g., siRNA and TKIS) increased their anti-leukemic potency by enhancement of their stability and/or concentration. MDR (multi-drug resistance). Free small drugs move into malignant cells through passive transmission across the cell membrane, and they come into contact with membrane proteins such as drug efflux pumps leading to less than optimum amounts in the target cell. Lipid packing density and velocity can affect diffusion through the membrane. Increased membrane fluidity implies considerable drug permeability by delivering therapeutic agents into cancer cells without relying on specific receptors or channels, and nanoparticles can circumvent this resistance mechanism.
Fig. 3
Fig. 3. Photodynamic therapy (PDT): ① the irradiation light would be utilized for the release of the drug encapsulated. ② The irradiation light excite the photosensitizer (PS) in the tumor tissue, causing the PS to form a ROS that kills tumor cells. Photothermic therapy (PTT): ③ upon radiation absorption, CNTs or metal nanoparticles can transform photon energy to thermal energy, which results in a temperature rise and subsequently makes cellular destruction.

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