18 research outputs found
Polyethyleneimine-Based Drug Delivery Systems for Cancer Theranostics
With the development of nanotechnology, various types of polymer-based drug delivery systems have been designed for biomedical applications. Polymer-based drug delivery systems with desirable biocompatibility can be efficiently delivered to tumor sites with passive or targeted effects and combined with other therapeutic and imaging agents for cancer theranostics. As an effective vehicle for drug and gene delivery, polyethyleneimine (PEI) has been extensively studied due to its rich surface amines and excellent water solubility. In this work, we summarize the surface modifications of PEI to enhance biocompatibility and functionalization. Additionally, the synthesis of PEI-based nanoparticles is discussed. We further review the applications of PEI-based drug delivery systems in cancer treatment, cancer imaging, and cancer theranostics. Finally, we thoroughly consider the outlook and challenges relating to PEI-based drug delivery systems
Antitumor Efficacy of Doxorubicin-Loaded Electrospun AttapulgiteâPoly(lactic-co-glycolic acid) Composite Nanofibers
Currently, cancer chemotherapeutic drugs still have the defects of high toxicity and low bioavailability, so it is critical to design novel drug release systems for cancer chemotherapy. Here, we report a method to fabricate electrospun drug-loaded organic/inorganic hybrid nanofibrous system for antitumor therapy applications. In this work, rod-like attapulgite (ATT) was utilized to load a model anticancer drug doxorubicin (DOX), and mixed with poly(lactic-co-glycolic acid) (PLGA) to form electrospun hybrid nanofibers. The ATT/DOX/PLGA composite nanofibers were characterized through various techniques. It is feasible to load DOX onto ATT surfaces, and the ATT/DOX/PLGA nanofibers show a smooth and uniform morphology with improved mechanical durability. Under neutral and acidic pH conditions, the loaded DOX was released from ATT/DOX/PLGA nanofibers in a sustained manner. In addition, the released DOX from the nanofibers could significantly inhibit the growth of tumor cells. Owing to the significantly reduced burst release profile and increased mechanical durability of the ATT/DOX/PLGA nanofibers, the designed organicâinorganic hybrid nanofibers may hold great promise as a nanoplatform to encapsulate different drugs for enhanced local tumor therapy applications
Three-Dimensional Printing Enabled Droplet Microfluidic Device for Real-Time Monitoring of Single-Cell Viability and Blebbing Activity
Droplet-based microfluidics with the characteristics of high throughput, low sample consumption, increasing reaction speed, and homogeneous volume control have been demonstrated as a useful platform for biomedical research and applications. The traditional fabrication methods of droplet microfluidics largely rely on expensive instruments, sophisticated operations, and even the requirement of an ultraclean room. In this manuscript, we present a 3D printing-based droplet microfluidic system with a specifically designed microstructure for droplet generation aimed at developing a more accessible and cost-effective method. The performance of droplet generation and the encapsulation capacity of the setup were examined. The device was further applied to measure the variation in cell viability over time and monitor the cellâs blebbing activity to investigate its potential ability and feasibility for single-cell analysis. The result demonstrated that the produced droplets remained stable enough to enable the long-time detection of cell viability. Additionally, cell membrane protrusions featuring the life cycle of bleb initiation, expansion, and retraction can be well-observed. Three-dimensional printing-based droplet microfluidics benefit from the ease of manufacture, which is expected to simplify the fabrication of microfluidics and expand the application of the droplet approach in biomedical fields
NIRâTriggered Phototherapy and Immunotherapy via an AntigenâCapturing Nanoplatform for Metastatic Cancer Treatment
Abstract Combined phototherapy and immunotherapy demonstrates strong potential in the treatment of metastatic cancers. An upconversion nanoparticle (UCNP) based antigenâcapturing nanoplatform is designed to synergize phototherapies and immunotherapy. In particular, this nanoplatform is constructed via selfâassembly of DSPEâPEGâmaleimide and indocyanine green (ICG) onto UCNPs, followed by loading of the photosensitizer rose bengal (RB). ICG significantly enhances the RBâbased photodynamic therapy efficiency of UCNP/ICG/RBâmal upon activation by a nearâinfrared (NIR) laser, simultaneously achieving selective photothermal therapy. Most importantly, tumorâderived protein antigens, arising from phototherapyâtreated tumor cells, can be captured and retained in situ, due to the functionality of maleimide, which further enhance the tumor antigen uptake and presentation by antigenâpresenting cells. The synergized photothermal, photodynamic, and immunological effects using lightâactivated UCNP/ICG/RBâmal induces a tumorâspecific immune response. In the experiments, intratumoral administration of UCNP/ICG/RBâmal, followed by noninvasive irradiation with an NIR laser, destroys primary tumors and inhibits untreated distant tumors, using a poorly immunogenic, highly metastatic 4T1 mammary tumor model. With the simultaneous use of antiâCTLAâ4, about 84% of the treated tumorâbearing mice achieve longâterm survival and 34% of mice develop tumorâspecific immunity. Overall, this antigenâcapturing nanoplatform provides a promising approach for the treatment of metastatic cancers
Targeted tumor dual mode CT/MR imaging using multifunctional polyethylenimine-entrapped gold nanoparticles loaded with gadolinium
We report the construction and characterization of polyethylenimine (PEI)-entrapped gold nanoparticles (AuNPs) chelated with gadolinium (Gd) ions for targeted dual mode tumor CT/MR imaging in vivo. In this work, polyethylene glycol (PEG) monomethyl ether-modified PEI was sequentially modified with Gd chelator and folic acid (FA)-linked PEG (FA-PEG) was used as a template to synthesize AuNPs, followed by Gd(III) chelation and acetylation of the remaining PEI surface amines. The formed FA-targeted PEI-entrapped AuNPs loaded with Gd (FA-Gd-Au PENPs) were well characterized in terms of structure, composition, morphology, and size distribution. We show that the FA-Gd-Au PENPs with an Au core size of 3.0ânm are water dispersible, colloidally stable, and noncytotoxic in a given concentration range. Thanks to the coexistence of Au and Gd elements within one nanoparticulate system, the FA-Gd-Au PENPs display a better X-ray attenuation property than clinical iodinated contrast agent (e.g. Omnipaque) and reasonable r1 relaxivity (1.1âmMâ1sâ1). These properties allow the FA-targeted particles to be used as an efficient nanoprobe for dual mode CT/MR imaging of tumors with excellent FA-mediated targeting specificity. With the demonstrated organ biocompatibility, the designed FA-Gd-Au PENPs may hold a great promise to be used as a nanoprobe for CT/MR dual mode imaging of different FA receptor-overexpressing tumors
Dendrimer-Modified MoS<sub>2</sub> Nanoflakes as a Platform for Combinational Gene Silencing and Photothermal Therapy of Tumors
Exploitation
of novel hybrid nanomaterials for combinational tumor therapy is challenging.
In this work, we synthesized dendrimer-modified MoS<sub>2</sub> nanoflakes
for combinational gene silencing and photothermal therapy (PTT) of
cancer cells. Hydrothermally synthesized MoS<sub>2</sub> nanoflakes
were modified with generation 5 (G5) polyÂ(amidoamine) dendrimers partially
functionalized with lipoic acid via disulfide bond. The formed G5-MoS<sub>2</sub> nanoflakes display good colloidal stability and superior
photothermal conversion efficiency and photothermal stability. With
the dendrimer surface amines on their surface, the G5-MoS<sub>2</sub> nanoflakes are capable of delivering Bcl-2 (B-cell lymphoma-2) siRNA
to cancer cells (4T1 cells, a mouse breast cancer cells) with excellent
transfection efficiency, inducing 47.3% of Bcl-2 protein expression
inhibition. <i>In vitro</i> cell viability assay data show
that cells treated with the G5-MoS<sub>2</sub>/Bcl-2 siRNA polyplexes
under laser irradiation have a viability of 21.0%, which is much lower
than other groups of single mode PTT treatment (45.8%) or single mode
of gene therapy (68.7%). Moreover, the super efficacy of combinational
therapy was further demonstrated by treating a xenografted 4T1 tumor
model <i>in vivo</i>. These results suggest that the synthesized
G5-MoS<sub>2</sub> nanoflakes may be employed as a potential nanoplatform
for combinational gene silencing and PTT of tumors
HER2-targeting two-dimensional black phosphorus as a nanoplatform for chemo-photothermal therapy in breast cancer
Trastuzumab (Tmab) targeted therapy or its combination with chemotherapy is normally insufficient to elicit a comprehensive therapeutic response owing to the inherent or acquired drug resistance and systemic toxicity observed in highly invasive HER2-positive breast cancer. In this study, we propose a novel approach that integrates photothermal therapy (PTT) with targeted therapy and chemotherapy, thereby achieving additive or synergistic therapeutic outcomes. We utilize PEGylated two-dimensional black phosphorus (2D BP) as a nanoplatform and photothermal agent to load chemotherapeutic drug mitoxantrone (MTO) and conjugate with Tmab (BP-PEG-MTO-Tmab). The in vitro and in vivo experiments demonstrated that the HER2-targeting BP-PEG-MTO-Tmab complexes exhibited desirable biocompatibility, safety and enhanced cancer cell uptake efficiency, resulting in increased accumulation and prolonged retention of BP and MTO within tumors. Consequently, the complex improved photothermal and chemotherapy treatment efficacy in HER2-positive cells in vitro and a subcutaneous tumor model in vivo, while minimized harm to normal cells and showed desirable organ compatibility. Collectively, our study provides compelling evidence for the remarkable efficacy of targeted and synergistic chemo-photothermal therapy utilizing all-in-one nanoparticles as a delivery system for BP and chemotherapeutic drug in HER2-positive breast cancer
Acetylated Polyethylenimine-Entrapped Gold Nanoparticles Enable Negative Computed Tomography Imaging of Orthotopic Hepatic Carcinoma
Developing
an effective computed tomography (CT) contrast agent
is still a challenging task for precise diagnosis of hepatic carcinoma
(HCC). Here, we present the use of acetylated polyethylenimine (PEI)-entrapped
gold nanoparticles (Ac-PE-AuNPs) without antifouling modification
for negative CT imaging of HCC. PEI was first linked to fluorescein
isothiocyanate (FI) and then utilized as a vehicle for the entrapment
of AuNPs. The particles were then acetylated to reduce its positive
surface potential. The designed Ac-PE-AuNPs were characterized by
various techniques. We find that the Ac-PE-AuNPs with a uniform size
distribution (mean diameter = 2.3 nm) are colloidally stable and possess
low toxicity in the studied range of concentration. Owing to the fact
that the particles without additional antifouling modification were
mainly gathered in liver, the Ac-PE-AuNPs could greatly improve the
CT contrast enhancement of normal liver, whereas poor CT contrast
enhancement appeared in liver necrosis region caused by HCC. As a
result, HCC could be easily and precisely diagnosed. The designed
Ac-PE-AuNPs were demonstrated to have biocompatibility through in
vivo biodistribution and histological studies, hence holding an enormous
potential to be adopted as an effective negative CT contrast agent
for diagnosis of hepatoma carcinoma