https://scholarlypublications.universiteitleiden.nl/access/item%3A3006177/view

Customizing poly(lactic-co-glycolic acid) particles for biomedical applications

Polymeric biomaterials have found widespread applications in nanomedicine, and poly(lactide-co-glycolide), (PLGA) in particular has been successfully implemented in numerous drug delivery formulations due to its synthetic malleability and biocompatibility. However, the need for preconception in these formulations is increasing, and this can be achieved by selection and elimination of design variables in order for these systems to be tailored for their specific applications. The starting materials and preparation methods have been shown to influence various parameters of PLGA-based nanocarriers and their implementation in drug delivery systems, while the implementation of computational simulations as a component of formulation studies can provide valuable information on their characteristics. This review provides a critical summary of the synthesis and applications of PLGA-based systems in bio-medicine and outlines experimental and computational design considerations of these systems.

The Design of Poly(lactide-co-glycolide) Nanocarriers for Medical Applications.

The field of nanotechnology has led to the development of many innovative strategies for effective detection and treatment of cancer, overcoming limitations associated with conventional cancer diagnosis and therapy. Multifunctional nanoparticle systems can integrate imaging, targeting and treatment moieties on the surface and in the core, resulting in targeted delivery of the imaging or treatment modalities, specifically to the tumor. Multifunctional nanoparticles also enable simultaneous delivery of multiple treatment agents, resulting in effective combinatorial therapeutic regimens against cancer. In this review, various multifunctional nanoparticle systems that feature a variety of targeting moieties for in vitro and/or in vivo cancer imaging and therapy are discussed.

Multifunctional Nanomaterials and Their Applications in Drug Delivery and Cancer Therapy.

Size-controlled biodegradable nanoparticles: preparation and size-dependent cellular uptake and tumor cell growth inhibition.

Janus nanoparticles (JNPs) refer to the integration of two or more chemically discrepant composites into one structure system. Studies into JNPs have been of significant interest due to their interesting characteristics stemming from their asymmetric structures, which can integrate different functional properties and perform more synergetic functions simultaneously. Herein, we present recent progress of Janus particles, comprehensively detailing fabrication strategies and applications. First, the classification of JNPs is divided into three blocks, consisting of polymeric composites, inorganic composites, and hybrid polymeric/inorganic JNPs composites. Then, the fabrication strategies are alternately summarized, examining self-assembly strategy, phase separation strategy, seed-mediated polymerization, microfluidic preparation strategy, nucleation growth methods, and masking methods. Finally, various intriguing applications of JNPs are presented, including solid surfactants agents, micro/nanomotors, and biomedical applications such as biosensing, controlled drug delivery, bioimaging, cancer therapy, and combined theranostics. Furthermore, challenges and future works in this field are provided.

Janus Nanoparticles: From Fabrication to (Bio)Applications.

Organic room temperature phosphorescence (RTP) materials with ultralong lifetime possess the remarkable advantage in bioimaging for elimination of background noise by characteristic time scale. However, most of RTP luminogens need to be excited by the harmful ultraviolet (UV) lamp, and exhibit green or yellow emission with shallow tissue penetration, constraining the in vivo bioimaging for further application in clinical diagnosis and pathological study. In this text, the much safer excitation process by sunlight and mobile phone flashlight is realized by organic luminogens with various electronic pull–push systems. Moreover, the bright red RTP emission with lifetime up to 344 ms is achieved by optimizing molecular geometry and electronic property. Especially, the mobile phone flashlight‐excited red afterglow imaging of lymph nodes in living mice has been realized for the first time, affording a safe and conventional approach to achieve the afterglow imaging of living mice with deep issue penetration and high signal‐to‐noise ratios.

Mobile Phone Flashlight‐Excited Red Afterglow Bioimaging

Sonodynamic therapy (SDT) holds growing promise in deep‐seated or large solid tumor treatment owing to its high tissue penetration depth ability; however, its therapeutic efficacy is often compromised due to the hypopermeable and hypoxic characteristics in the tumor milieu. Herein, a semiconducting polymer nanoparticle (SPNC) that synergistically enhances tumor penetration and alleviates tumor hypoxia is reported for sonodynamic therapy of large solid tumors. SPNC comprises a semiconducting polymer nanoparticle core as a sonodynamic converter coated with a poly (ethylene glycol) corona. An oxygen‐modulating enzyme, catalase, is efficiently conjugated to the surface of nanoparticles via the coupling reaction. Superior to its counterpart SPNCs (SPNC2 (84 nm) and SPNC3 (134 nm)), SPNC with the smallest size (SPNC1 (35 nm)) can efficiently penetrate throughout the tumor interstitium to alleviate whole tumor hypoxia in a large solid tumor model. Upon ultrasound (US) irradiation, SPNC1 can remotely generate sufficient singlet oxygen to eradicate tumor cells at a deep‐tissue depth. Such a single treatment of SPNC1‐medicated sonodynamic therapy effectively inhibits tumor growth in a large solid tumor mouse model. Therefore, this study provides a generalized strategy to synergistically overcome both poor penetration and hypoxia of large tumors for enhanced cancer treatment.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202104125

Enhancing Penetration Ability of Semiconducting Polymer Nanoparticles for Sonodynamic Therapy of Large Solid Tumor

X-ray-induced photodynamic therapy utilizes penetrating X-rays to activate reactive oxygen species in deep tissues for cancer treatment, which combines the advantages of photodynamic therapy and radiotherapy. Conventional therapy usually requires heavy-metal-containing inorganic scintillators and organic photosensitizers to generate singlet oxygen. Here, we report a more convenient strategy for X-ray-induced photodynamic therapy based on a class of organic phosphorescence nanoscintillators, that act in a dual capacity as scintillators and photosensitizers. The resulting low dose of 0.4 Gy and negligible adverse effects demonstrate the great potential for the treatment of deep tumours. These findings provide an optional route that leverages the optical properties of purely organic scintillators for deep-tissue photodynamic therapy. Furthermore, these organic nanoscintillators offer an opportunity to expand applications in the fields of biomaterials and nanobiotechnology. 

/pdf/organic-phosphorescent-nanoscintillator-for-low-dose-x-ray-1q0tmxfz.pdf

Organic phosphorescent nanoscintillator for low-dose X-ray-induced photodynamic therapy

We present a simple, yet versatile strategy for the fabrication of uniform biodegradable polymer nanoparticles (NPs) with controllable sizes by a hand-driven membrane-extrusion emulsification approach. The size and size distribution of the NPs can be easily tuned by varying the experimental parameters, including initial polymer concentration, surfactant concentration, number of extrusion passes, membrane pore size, and polymer molecular weight. Moreover, hydrophobic drugs (e.g., paclitaxel (PTX)) and inorganic NPs (e.g., quantum dots (QDs) and magnetic NPs (MNPs)) can be effectively and simultaneously encapsulated into the polymer NPs to form the multifunctional hybrid NPs through this facile route. These PTX-loaded NPs exhibit high encapsulation efficiency and drug loading density as well as excellent drug sustained release performance. As a proof of concept, the A875 cell (melanoma cell line) experiment in vitro, including cellular uptake analysis by fluorescence microscope, cytotoxicity analysis of NPs, and magnetic resonance imaging (MRI) studies, indicates that the PTX-loaded hybrid NPs produced by this technique could be potentially applied as a multifunctional delivery system for drug delivery, bio-imaging, and tumor therapy, including malignant melanoma therapy.

https://iopscience.iop.org/article/10.1088/0957-4484/24/45/455302/pdf

Min Wu

Papers

Mobile Phone Flashlight‐Excited Red Afterglow Bioimaging

Enhancing Penetration Ability of Semiconducting Polymer Nanoparticles for Sonodynamic Therapy of Large Solid Tumor

Organic phosphorescent nanoscintillator for low-dose X-ray-induced photodynamic therapy

Multifunctional biodegradable polymer nanoparticles with uniform sizes: generation and in vitro anti-melanoma activity

Synthesis of polymer–inorganic patchy microcapsules with tunable patches