An Integrated Tumor Microenvironment Responsive Polymeric Micelle for Smart Drug Delivery and Effective Drug Release

Physiological characteristics of diseases bring about both challenges and opportunities for targeted drug delivery. Various drug delivery platforms have been devised ranging from macro- to micro- and further into the nanoscopic scale in the past decades. Recently, the favorable physicochemical properties of nanomaterials, including long circulation, robust tissue and cell penetration attract broad interest, leading to extensive studies for therapeutic benefits. Accumulated knowledge about the physiological barriers that affect the in vivo fate of nanomedicine has led to more rational guidelines for tailoring the nanocarriers, such as size, shape, charge, and surface ligands. Meanwhile, progresses in material chemistry and molecular pharmaceutics generate a panel of physiological stimuli-responsive modules that are equipped into the formulations to prepare “smart” drug delivery systems. The capability of harnessing physiological traits of diseased tissues to control the accumulation of or drug release from nanomedicine has further improved the controlled drug release profiles with a precise manner. Successful clinical translation of a few nano-formulations has excited the collaborative efforts from the research community, pharmaceutical industry, and the public towards a promising future of smart drug delivery.

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Smart drug delivery systems: from fundamentals to the clinic

Chemical Communications ◽

10.1039/c4cc01429d ◽

2014 ◽

Vol 50 (58) ◽

pp. 7743-7765 ◽

Cited By ~ 210

Author(s):

Carmen Alvarez-Lorenzo ◽

Angel Concheiro

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Medical Devices ◽

Smart Materials ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Smart Drug ◽

Smart Drug Delivery

Smart materials can endow implantable depots, targetable nanocarriers and insertable medical devices with activation-modulated and feedback-regulated control of drug release.

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A Smart Drug Delivery System from Charge-Conversion Polymer-Drug Conjugate for Enhancing Tumor Therapy and Tunable Drug Release

Macromolecular Bioscience ◽

10.1002/mabi.201300337 ◽

2014 ◽

Vol 14 (4) ◽

pp. 485-490 ◽

Cited By ~ 16

Author(s):

Hailong Huang ◽

Yapeng Li ◽

Zongpeng Sa ◽

Yuan Sun ◽

Yuzhen Wang ◽

...

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Drug Delivery System ◽

Delivery System ◽

Tumor Therapy ◽

Drug Conjugate ◽

Smart Drug ◽

Smart Drug Delivery

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A Smart Drug Delivery System Based on Biodegradable Chitosan/Poly(allylamine hydrochloride) Blend Films

Pharmaceutics ◽

10.3390/pharmaceutics12020131 ◽

2020 ◽

Vol 12 (2) ◽

pp. 131 ◽

Cited By ~ 9

Author(s):

Muhammad Sohail Sarwar ◽

Qingrong Huang ◽

Abdul Ghaffar ◽

Muhmmad Amin Abid ◽

Muhammad Sohail Zafar ◽

...

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Simulated Gastric Fluid ◽

Sustained Drug Release ◽

Water Contact ◽

Blend Films ◽

Allylamine Hydrochloride ◽

Smart Drug ◽

Smart Drug Delivery

The amalgamation of natural polysaccharides with synthetic polymers often produces fruitful results in the area of drug delivery due to their biodegradable and biocompatible nature. In this study, a series of blend films composed of chitosan (CS)/poly(allylamine hydrochloride) (PAH) in different compositions were prepared as smart drug delivery matrices. The properties of these polymeric films were then explored. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) analysis confirmed an intermolecular hydrogen bonding between CS and PAH. Atomic force microscopy (AFM) revealed improvements in surface morphology as the percentage of PAH in the blend films increased up to 60% (w/w). Water contact angle (WCA) ranged between 97° to 115°, exhibiting the hydrophobic nature of the films. Two films were selected, CTH-1 (90% CS and 10% PAH) and CTH-2 (80% CS and 20% PAH), to test for in vitro cumulative drug release (%) at 37 ± 0.5 °C as a function of time. It was revealed that for simulated gastric fluid (SGF) with pH 1.2, the cumulative drug release (CDR) for CTH-1 and CTH-2 was around 88% and 85% in 50 min, respectively. Both films converted into gel-like material after 30 min. On the other hand, in pH 7.4 phosphate buffer saline (PBS) solution, the maximum CDR for CTH-1 and CTH-2 was 93% in 90 min and 98% in 120 min, respectively. After 120 min, these films became fragments. Sustained drug release was observed in PBS, as compared to SGF, because of the poor stability of the films in the latter. These results demonstrate the excellent potential of blend films in sustained-release drug delivery systems for hydrophilic or unstable drugs.

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Therapeutic impacts of enzyme-responsive smart nanobiosystems

Bioimpacts ◽

10.15171/bi.2020.01 ◽

2019 ◽

Vol 10 (1) ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

Marziyeh Fathi ◽

Azam Safary ◽

Jaleh Barar

Keyword(s):

Drug Delivery ◽

Controlled Release ◽

Tumor Microenvironment ◽

Clinical Outcomes ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Release Behavior ◽

Site Specific ◽

Smart Drug ◽

Smart Drug Delivery

An important arena of the sophisticated nanosystems (NSs) is the combination of the responsive features of NSs with the biocatalytic properties of enzymes. The development of such smart drug delivery systems (DDSs) has seminal effectiveness in targeting, imaging, and monitoring of cancer. These NSs can exhibit site-specific delivery of the toxic cargo in response to the endogenous/exogenous stimuli. Enzyme responsive/targeted DDSs display enhanced accumulation of cargo molecules in the tumor microenvironment (TME) with a spatiotemporal controlled-release behavior. Based on the unique features of enzyme responsive/targeted DDSs, they offer incredible promise in overcoming some limitations of the currently used conventional DDSs. Taken all, targeting TME with the enzyme-responsive targeted DDSs may lead to versatile clinical outcomes in various malignancies.

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Synergistic Cascade Strategy Based on Modifying Tumor Microenvironment for Enhanced Breast Cancer Therapy

10.21203/rs.3.rs-700346/v1 ◽

2021 ◽

Author(s):

Huan Zhang ◽

Jinshun Xu ◽

Binyang Gao ◽

Hong Wang ◽

Jianbo Huang ◽

...

Keyword(s):

Breast Cancer ◽

Drug Delivery ◽

Tumor Microenvironment ◽

Drug Delivery System ◽

Delivery System ◽

Nanoparticle Uptake ◽

Mild Hyperthermia ◽

Mw Irradiation ◽

Smart Drug ◽

Smart Drug Delivery

Abstract Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with very few treatment options. Although tumor-targeted nanomedicines hold great promise for the treatment of TNBC, the tumor microenvironment (TME) continues to be a major cause of failure in nanotherapy and immunotherapy. To overcome this barrier, we designed a new synergistic cascade strategy (SCS) that uses mild hyperthermia and smart drug delivery system (SDDS) to alter TME resistance in order to improve drug delivery and therapeutic efficacy of TNBC.Methods: Mild hyperthermia was produced by microwave (MW) irradiation. SDDS were formulated with thermosensitive polymer-lipid nanoparticles (HA-BNPs@Ptx), composed of polymer PLGA, phospholipid DPPC, hyaluronic acid (HA, a differentiation-44 targeted molecule, also known as CD44), 1-butyl-3-methylimidazolium-L-lactate (BML, a MW sensitizer) and paclitaxel (Ptx, chemotherapy drug). 4T1 breast tumor-bearing mice were treated with two-step MW combined with HA-BNPs@Ptx. Tumors in mice were pretreated with 1st MW irradiation prior to nanoparticle injection to modify TME and promote TME and promoting nanoparticle uptake and retention. The 2nd MW irradiation was performed on the tumor 24 h after the injection HA-BNPs@Ptx to produce a synergistic cascade effect through activating BML, thus enhancing hyperthermia effect, and instantly releasing Ptx at the tumor site.Results: Multifunctional CD44-targeted nanoparticles HA-BNPs@Ptx were successfully prepared and validated in-vitro. After the 1st MW irradiation of tumors in mice, the intratumoral perfusion increased by 2 times and the nanoparticle uptake augmented by 7 times. With the 2nd MW irradiation, remarkable anti-tumor effects were obtained with the inhibition rate up to 88%. In addition, immunohistochemical analysis showed that SCS therapy could not only promote the tumor cells apoptosis, trigger the immune response of cytotoxic T lymphocytes, but also significantly reduce the lung metastasis. Conclusions: The SCS using mild hyperthermia combined with smart drug delivery system, can significantly improve the efficacy of TNBC treatment in mice by modifying TME and hyperthermia-mediated EPR effects.

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Novel Thioacetal-Bridged Hollow Mesoporous Organosilica Nanoparticles with ROS-Responsive Biodegradability for Smart Drug Delivery

NANO ◽

10.1142/s1793292019501418 ◽

2019 ◽

Vol 14 (11) ◽

pp. 1950141 ◽

Cited By ~ 1

Author(s):

Zeyang Lin ◽

Long Xu ◽

Jianfeng Zhang ◽

Zhou Li ◽

Jinshun Zhao

Keyword(s):

Electron Microscopy ◽

Drug Delivery ◽

Drug Release ◽

Silica Nanoparticles ◽

Drug Delivery System ◽

Delivery System ◽

Mesoporous Organosilica ◽

Smart Drug ◽

Smart Drug Delivery

Intelligent, efficient silica nanoparticles for drug delivery system in cancer therapy have a great application potential, but the biodegradability of silica nanoparticles becomes an intractable hindrance. In this work, novel reactive oxygen species (ROS)-responsive hollow mesoporous organosilica nanoparticles (HMONs) coated with polydopamine (PDA) biofilm and amino-terminated methoxy poly(ethylene glycol) (mPEG-NH[Formula: see text] were synthesized and applied in the smart drug delivery system (HMONs@PDA-mPEG) for the delivery of doxorubicin (DOX). The nanostructures and morphologies of nanoparticles were characterized by Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), N2 adsorption/desorption, dynamic light scattering (DLS) and thermogravimetric analysis. Based on the “chemical homology” mechanism, physiologically active thioacetal-bridged silsesquioxane was molecularly incorporated into the framework of silica nanoparticles to form ROS-responsive HMONs, which was verified by the in vitro degradation experiment. The in vitro drug release profiles showed a synergistically pH-dependent and ROS-responsive drug release effect. MTT assay toward A549 cells demonstrated that drug carriers had a biocompatibility, and DOX-loaded nanoparticles (DNs) presented a concentration-dependent and time-dependent cell growth inhibition effect. In summary, the novel ROS-responsive HMONs@PDA-mPEG had a promising application as a smart drug delivery system in biomedical field.

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Adult Stem Cells and Biocompatible Scaffolds as Smart Drug Delivery Tools for Cardiac Tissue Repair

Current Medicinal Chemistry ◽

10.2174/09298673113209990032 ◽

2013 ◽

Vol 20 (28) ◽

pp. 3429-3447 ◽

Cited By ~ 9

Author(s):

Stefania Pagliari ◽

Sara Romanazzo ◽

Diogo Mosqueira ◽

Perpetua Pinto-do-O ◽

Takao Aoyagi ◽

...

Keyword(s):

Drug Delivery ◽

Stem Cells ◽

Tissue Repair ◽

Adult Stem Cells ◽

Cardiac Tissue ◽

Smart Drug ◽

Smart Drug Delivery

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Advances in Nanoparticles as Anticancer Drug Delivery Vector: Need of this Century

Current Pharmaceutical Design ◽

10.2174/1381612826666200203124330 ◽

2020 ◽

Vol 26 (15) ◽

pp. 1637-1649 ◽

Cited By ~ 3

Author(s):

Imran Ali ◽

Sofi D. Mukhtar ◽

Heyam S. Ali ◽

Marcus T. Scotti ◽

Luciana Scotti

Keyword(s):

Drug Delivery ◽

Anticancer Drug ◽

Medical Science ◽

Drug Carriers ◽

Anticancer Drug Delivery ◽

Ph Values ◽

Delivery Vector ◽

Future Challenges ◽

Smart Drug ◽

Smart Drug Delivery

Background: Nanotechnology has contributed a great deal to the field of medical science. Smart drugdelivery vectors, combined with stimuli-based characteristics, are becoming increasingly important. The use of external and internal stimulating factors can have enormous benefits and increase the targeting efficiency of nanotechnology platforms. The pH values of tumor vascular tissues are acidic in nature, allowing the improved targeting of anticancer drug payloads using drug-delivery vectors. Nanopolymers are smart drug-delivery vectors that have recently been developed and recommended for use by scientists because of their potential targeting capabilities, non-toxicity and biocompatibility, and make them ideal nanocarriers for personalized drug delivery. Method: The present review article provides an overview of current advances in the use of nanoparticles (NPs) as anticancer drug-delivery vectors. Results: This article reviews the molecular basis for the use of NPs in medicine, including personalized medicine, personalized therapy, emerging vistas in anticancer therapy, nanopolymer targeting, passive and active targeting transports, pH-responsive drug carriers, biological barriers, computer-aided drug design, future challenges and perspectives, biodegradability and safety. Conclusions: This article will benefit academia, researchers, clinicians, and government authorities by providing a basis for further research advancements.

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