A functional nanocarrier that copenetrates extracellular matrix and multiple layers of tumor cells for sequential and deep tumor autophagy inhibitor and chemotherapeutic delivery

Wang, Yang; Qiu, Yue; Yin, Sheng; Zhang, Li; Shi, Kai; Gao, Huile; Zhang, Zhirong; He, Qin

doi:10.1080/15548627.2016.1256523

Cited by 16 publications

(9 citation statements)

References 58 publications

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“…To deliver chemotherapeutic agents into the deep tumor, Wang et al designed a core-shell nanocarrier in which the reversible swelling-shrinking core was loaded with an anticancer drug (DOX) and the degradable gelatin shell was used to encapsulate the autophagy inhibitor 3-methyladenine (3-MA). [73] The gelatin shell could be degraded by the overexpressed MMP-2 in the tumor region to release the encapsulated 3-MA. Then, the exposed small core could become larger upon exposure to the acidic lysosome environment of cancer cells, ultimately resulting in the rapid release of DOX to effectively kill the autophagy-inhibited cancer cells.…”

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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Section: Nss With Multiple Transformationsmentioning

confidence: 99%

Size‐Transformable Nanostructures: From Design to Biomedical Applications

et al. 2020

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“…developed nanocarriers composed of a pH‐triggered reversible swelling‐shrinking core to encapsulate DOX and an MMP2‐cleavable gelatin shell to load 3‐methyladenine (3‐MA) which is an autophagy inhibitor because autophagy compromised the antitumor efficacy of DOX. They showed that 3‐MA released at the ECM and entered tumor cells to inhibit their autophagy after MMP2‐induced degradation of the shell, then the exposed core could diffuse along the pores of ECM to deliver DOX into deep tumors . They attempted to explore the role of autophagy in breast cancer metastasis and developed tumor‐activatable particles to co‐deliver DOX and autophagy inhibitor chloroquine phosphate (CQ), termed D/PSP@CQ/CaP.…”

Section: Nanocarriersmentioning

confidence: 99%

Organic Nanocarriers for Delivery and Targeting of Therapeutic Agents for Cancer Treatment

Peng

Bariwal

Kumar

et al. 2020

Advanced Therapeutics

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Nanocarriers have the capability to deliver a variety of drugs to disease sites. Different biological barriers prevent the successful delivery of nanoformulations to target sites, thereby limiting effective therapeutic response. Although numerous efforts have been made to design novel nanocarriers by incorporating various functionalities to get better therapies, most strategies have failed to translate drug delivery systems to the clinic. Impediments such as the incapability to hold drugs stably in nanocarriers during circulation, non‐specific distribution, and inadequate delivery of therapeutic agents to target sites due to complex tumor microenvironment remain a challenge. Herein, different organic polymer and lipid‐based nanocarriers and their encouraging therapeutic effectiveness to treat cancer are discussed. Recent development in multifunctional and stimuli sensitive nanocarriers is also highlighted. Finally, the challenges and innovative strategies to overcome various obstacles and limitations for their successful translation into the clinic are discussed.

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“…In a study conducted by Wang et al [327] a nanocarrier was used that could simultaneously overcome the double physiological barriers of tumors. The nanocarrier was designed as a pH-triggered reversible swelling-shrinking core and a matrix metallopeptidase 2 (MMP2) degradable shell for co-delivery of chemotherapeutics DOX and autophagy inhibitors (3-MA).…”

Section: Co-delivery Of Autophagy Inducers/inhibitors and Chemothmentioning

confidence: 99%

Autophagy Modulators: Mechanistic Aspects and Drug Delivery Systems

et al. 2019

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Autophagy modulation is considered to be a promising programmed cell death mechanism to prevent and cure a great number of disorders and diseases. The crucial step in designing an effective therapeutic approach is to understand the correct and accurate causes of diseases and to understand whether autophagy plays a cytoprotective or cytotoxic/cytostatic role in the progression and prevention of disease. This knowledge will help scientists find approaches to manipulate tumor and pathologic cells in order to enhance cellular sensitivity to therapeutics and treat them. Although some conventional therapeutics suffer from poor solubility, bioavailability and controlled release mechanisms, it appears that novel nanoplatforms overcome these obstacles and have led to the design of a theranostic-controlled drug release system with high solubility and active targeting and stimuli-responsive potentials. In this review, we discuss autophagy modulators-related signaling pathways and some of the drug delivery strategies that have been applied to the field of therapeutic application of autophagy modulators. Moreover, we describe how therapeutics will target various steps of the autophagic machinery. Furthermore, nano drug delivery platforms for autophagy targeting and co-delivery of autophagy modulators with chemotherapeutics/siRNA, are also discussed.

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A functional nanocarrier that copenetrates extracellular matrix and multiple layers of tumor cells for sequential and deep tumor autophagy inhibitor and chemotherapeutic delivery

Cited by 16 publications

References 58 publications

Size‐Transformable Nanostructures: From Design to Biomedical Applications

Size‐Transformable Nanostructures: From Design to Biomedical Applications

Organic Nanocarriers for Delivery and Targeting of Therapeutic Agents for Cancer Treatment

Autophagy Modulators: Mechanistic Aspects and Drug Delivery Systems

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