Transforming Complexity to Simplicity: Protein-Like Nanotransformer for Improving Tumor Drug Delivery Programmatically

Xiong, Hui; Wang, Zihan; Wang, Cheng; Yao, Jing

doi:10.1021/acs.nanolett.9b05008

Cited by 60 publications

(47 citation statements)

References 40 publications

(56 reference statements)

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“…As an emerging therapeutic strategy, gas therapy has attracted increasing attention in cancer treatment. [1] Therapeutic gases such as carbon monoxide (CO), [2] nitric oxide (NO), [3] hydrogen sulfide (H 2 S), [4] oxygen (O 2 ), [5] and sulfur dioxide (SO 2 ) [6] play important roles in various physiological process in cells, tissues or organisms, thus exhibiting great potential in various therapies including cancer therapy. O 2 has been the most widely used gas molecule during cancer therapy for overcoming hypoxia and contributing enhanced photodynamic therapy or sonodynamic therapy.…”

Section: Introductionmentioning

confidence: 99%

Self‐Propelled Asymmetrical Nanomotor for Self‐Reported Gas Therapy

Yue

Yang

et al. 2021

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Gas therapy has emerged as a new therapeutic strategy in combating cancer owing to its high therapeutic efficacy and biosafety. However, the clinical translation of gas therapy remains challenging due to the rapid diffusion and limited tissue penetration of therapeutic gases. Herein, a self‐propelled, asymmetrical Au@MnO2 nanomotor for efficient delivery of therapeutic gas to deep‐seated cancer tissue for enhanced efficacy of gas therapy, is reported. The Au@MnO2 nanoparticles (NPs) catalyze endogenous H2O2 into O2 that propels NPs into deep solid tumors, where SO2 prodrug is released from the hollow NPs owing to the degradation of MnO2 shells. Fluorescein isothiocyanate (FITC) is conjugated onto the surface of Au via caspase‐3 responsive peptide (DEVD) and the therapeutic process of gas therapy can be optically self‐reported by the fluorescence of FITC that is turned on in the presence of overexpressed caspase‐3 as an apoptosis indicator. Au@MnO2 nanomotors show self‐reported therapeutic efficacy and high biocompatibility both in vitro and in vivo, offering important new insights to the design and development of novel nanomotors for efficient payload delivery into deep tumor tissue and in situ monitoring of the therapeutic process.

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Section: Introductionmentioning

confidence: 99%

Self‐Propelled Asymmetrical Nanomotor for Self‐Reported Gas Therapy

Yue

Yang

et al. 2021

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“…Lysosomes are highly acidic and enzyme-abundant cellular organelles involved in the degradation and recycling of components derived from the extracellular space through endocytosis/phagocytosis and autophagy from the cytoplasm, which is viewed as lipid bilayer-bounded "waste incinerators." [59] Owing to their regular fusion with late endosomes or autophagosomes, lysosomes are characterized by aberrant acid (pH = 4.5-5.5) [60] and specific hydrolases, such as cathepsin B and legumain, within the cell. [61] Presently, it is widely accepted that nanoplatforms are usually entrapped in the lysosomes of cancer cells after cellular uptake, and this harsh environment drastically attenuates the therapeutic efficiency through acid-and enzymemediated NP degradation.…”

Section: Lysosomal Nanogatekeepersmentioning

confidence: 99%

Smart Nanogatekeepers for Tumor Theranostics

Zhang

Chen

et al. 2021

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early tumor mass efficiently, but a single surgical approach seems incompetent for advanced tumor tissues with serious distant metastasis. Surgery cannot completely remove all primary and metastatic tumor cells, thereby generating a high recurrence risk. [2] High-energy radioactive rays are utilized to destroy DNA and protein structures and inhibit there functions in these exposed tumor cells. However, it should be noted that this local irradiationtriggered therapy modality does not distinguish cancer from other tissues, which could induce fatal destruction in circumambient normal tissues. Immunotherapy is an emerging modality that relies on the human immune system and provides a robust defense against advanced and metastatic tumors. [3] Immune checkpoint blockade (ICB) therapy, for example, promotes a systemic immune response that suppresses tumor growth and recurrence by blocking the overexpressed programmed cell death ligand 1 (PD-L1) [4] and CD47 [5] in tumor cells, or cytotoxic T lymphocyte (CTL) associated antigen 4 (CTLA-4) in T cells. [6] Several ICB antibodies, such as pembrolizumab and nivolumab, have been approved by the Food and Drug Administration of the USA (FDA) to treat metastatic colorectal cancer (CRC). [7] Unfortunately, clinical trials revealed that only a fraction of patients with clinical cancer respond to this emerging immunotherapy [8] although this poor efficiency is mainly ascribed to insufficient T cell infiltration [9] and undesirable immunosuppressive microenvironments. [10] Compared to surgery, radiotherapy, and immunotherapy, chemotherapy is preferable as monotherapy or synergetic therapy with the above modalities for cancer treatment. In general, current chemotherapeutic formulations are categorized as solutions and nanoformulations. For example, chemotherapeutic solutions such as Taxel and Doxil are used clinically, but the undesirable selectivity and serious toxicity significantly hinder further application. Compared to solutions, nanoformulations exhibit increased drug accumulation in tumor tissue due to the enhanced permeability and retention (EPR) effect. Specifically, paclitaxel (PTX)-derived Nanoxel shows a higher tumor regression profile than Taxol solution, with improved safety. [11] In addition to EPR-mediated passive accumulation, a liganddirected targeting strategy is also employed in developing nanoparticle (NP) delivery systems as this enables specific ligand-receptor interactions for NP accumulation. [12] To date, numerous tumor microenvironment-sensitive deshielding nanosystems have been fabricated to realize stealth-targeting Nanoparticulate drug delivery systems (nano-DDSs) are required to reliably arrive and persistently reside at the tumor site with minimal off-target side effects for clinical theranostics. However, due to the complicated environment and high interstitial pressure in tumor tissue, they can return to the bloodstream and cause secondary side effects in normal organs. Recently, a number of nanogatekeepers have been engineered via structure-transf...

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“…Inspired by the denaturation and renaturation of proteins, Xiong et al designed an instantaneously transformable NS (DTIG) composed of DOX, tannic acid, and ICG, and this NS possessed proton-triggered hydrophobic-hydrophilic transition capacity and size conversion properties. [72] DTIG possesses a suitable particle size of ≈70 nm for blood circulation, and it can be altered into a larger and more hydrophobic NS in the weakly acidic tumor microenvironment to increase their internalization ability into cancer cells. The transformation process was then further accelerated in a more acidic lysosomal environment, and much larger NSs possessing sizes greater than 1.5 µm were formed in the lysosomes, ultimately enabling them to escape from lysosomes by destroying the lysosomal membrane.…”

Section: Nss With Multiple Transformationsmentioning

confidence: 99%

Size‐Transformable Nanostructures: From Design to Biomedical Applications

et al. 2020

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AuNPs) with a size of 50 nm were more easily internalized into mammalian cells than were AuNPs of other sizes (14, 30, 74, and 100 nm). [3] Jiang et al. demonstrated that gold and silver nanoparticlemediated cellular responses were size dependent. [4] Wang et al. reported that the size of micelles significantly influenced their blood circulation time, tumor accumulation, and tumor penetration. [5] Additionally, nanoparticles exhibited sizedependent antibacterial activity and biofilm penetration properties. [6] Typically, small NSs possess the advantages of: 1) high surface-to-volume ratio that provides them with a large surface by which to contact the biological environment, [6b] 2) excellent biosafety and biocompatibility owing to their ease of excretion from living systems, [7] 3) capability to cross intracellular or in vivo barriers such as cell nuclear membranes [8] and blood-brain barriers (BBBs) [9] that allows them to enter these difficult-to-reach regions, and 4) strong penetration ability to reach the depths of solid tumors [10] and bacterial biofilms. [11] In comparison, large NSs typically exhibit long tissue retention periods [12] and slow exocytosis rates from the cells, [13] both of which are ideal for long-term imaging and effective treatment. Moreover, certain large NSs possess more favorable properties than do small ones in regard to enhanced theranostics. [14] To achieve satisfactory theranostic performance in addition to acceptable biosafety, NSs should exhibit the merits of both small and large NSs, and these merits include long-term retention, deep penetration, and rapid clearance. Among the various strategies used for overcoming the size paradox, utilizing size-transformable NSs has been demonstrated to be an available and effective method, as these types of NSs can easily integrate the advantages of small and large NSs. They can behave as small NSs for tissue penetration, rapid clearance, and crossing biological barriers, and can act as large NSs to meet the demands of long-term retention at the targeted sites. During or after the size transformation in these NSs, the loaded drugs within the NSs can be exposed or released from the system, ultimately enabling the transformable NSs to provide a versatile platform for disease theranostics. Based on their superior properties, a great deal of progress in regard to the design and applications of size-transformable NSs has occurred over the last several decades. [15] In this review, we focus on summarizing the design methods and biomedical applications of two types of size-transformable NSs, specifically the size-decreasing and size-increasing NSs. In addition to the The size of nanostructures (NSs) strongly affects their chemical and physical properties and further impacts their actions in biological systems. Both small and large NSs possess respective advantages for disease theranostics, and this therefore presents a paradox when choosing NSs with suitable sizes. To overcome this challenge, size-transformable NSs have emerged as a powerful tool,...

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Transforming Complexity to Simplicity: Protein-Like Nanotransformer for Improving Tumor Drug Delivery Programmatically

Cited by 60 publications

References 40 publications

Self‐Propelled Asymmetrical Nanomotor for Self‐Reported Gas Therapy

Self‐Propelled Asymmetrical Nanomotor for Self‐Reported Gas Therapy

Smart Nanogatekeepers for Tumor Theranostics

Size‐Transformable Nanostructures: From Design to Biomedical Applications

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