The worldwide steady increase in the number of cancer patients motivates the development of innovative drug delivery systems for combination therapy as an effective clinical modality for cancer treatment. Here, we explored a design concept based on poly(ethylene glycol)-b-poly(2-(dimethylamino)ethyl methacrylate)-b-poly(2-hydroxyethyl methacrylate-formylbenzoic acid) [PEG-b-PDMAEMA-b-P(HEMA-FBA)] for the dual delivery of doxorubicin (DOX) and GTI2040 (an antisense oligonucleotide for ribonucleotide reductase inhibition) to MCF-7 breast cancer cells. PEG-b-PDMAEMA-b-PHEMA, the precursor copolymer, was prepared through chain extensions from a PEG-based macroinitiator via two consecutive atom transfer radical polymerization (ATRP) steps. Then, it was modified at the PHEMA block with 4-formylbenzoic acid (FBA) to install reactive aldehyde moieties. A pH-responsive polymer–drug conjugate (PDC) was obtained by conjugating DOX to the polymer structure via acid-labile imine linkages, and subsequently self-assembled in an aqueous solution to form DOX-loaded self-assembled nanoparticles (DOX-SAN) with a positively charged shell. DOX-SAN condensed readily with negatively charged GTI2040 to form GTI2040/DOX-SAN nanocomplexes. Gel-retardation assay confirmed the affinity between GTI2040 and DOX-SAN. The GTI2040/DOX-SAN nanocomplex at N/P ratio of 30 exhibited a volume-average hydrodynamic size of 136.4 nm and a zeta potential of 21.0 mV. The pH-sensitivity of DOX-SAN was confirmed by the DOX release study based on the significant cumulative DOX release at pH 5.5 relative to pH 7.4. Cellular uptake study demonstrated favorable accumulation of GTI2040/DOX-SAN inside MCF-7 cells compared with free GTI2040/DOX. In vitro cytotoxicity study indicated higher therapeutic efficacy of GTI2040/DOX-SAN relative to DOX-SAN alone because of the downregulation of the R2 protein of ribonucleotide reductase. These outcomes suggest that the self-assembled pH-responsive triblock copolymer is a promising platform for combination therapy, which may be more effective in combating cancer than individual therapies.

Background: Sepsis is a life-threatening illness in which the widespread infection triggers body’s immune system to produce excess amount of several chemicals that leads to organ failure and eventually death. The prevalent strategy to treat sepsis is the early detection of infection source and prescribing specific antibiotics. With current treatments, sepsis causes nearly 270,000 death in Americans each year which is equivalent to 1 in 3 death in hospitals. Recently, the extracorporeal device that could adsorb inflammatory chemicals form the bloodstream has gain tremendous attentions.

Specific aim: Previously, we have developed the novel telodendrimer (TD) nanotrap (NT) technology based on the commercial size-exclusive microgels. Here, we aim to develop polyethylene glycol (PEG) microgels with relatively low cost of production and tailorable properties.

Method: Inverse suspension radical polymerization (ISRP) was used to synthesize microgels with tailored properties. We followed classical parametric study to investigate ISRP process. Various microscopy and imaging techniques were used to obtain the size distribution of microgels. Three different strategies were established to introduce telodendrimer in the microgels structure. The functional microgels were tested for their efficiency to adsorb various model proteins and septic patient cytokines.

Conclusions: The TD-functionalized microgels showed size-exclusive adsorption for the model proteins. It also showed good efficiency in cytokine removal from a septic patient plasma. Overall, the results suggest that PEG microgels can be produced at various scales and desirable properties, making them a potential material for a hemoperfusion device.

• Authors: Nima Shahkaramipour, Amin Jafari, Thien Tran, Christopher M Stafford, Chong Cheng, Haiqing Lin

• Year: 2020

• Journal: Journal of membrane science

• Description: Superhydrophilic zwitterions have been extensively exploited for surface modification to improve antifouling properties. However, it remains challenging to form layers of <20 nm with high zwitterion content on the surfaces with different degrees of hydrophilicity. We demonstrate that amine-functionalized sulfobetaine (SBAm) can be co-deposited with dopamine on ultrafiltration (UF) membranes, leading to a thickness of 10 nm to 50 nm and an SBAm content of up to 31 mass% in the coating layers. The covalently grafted SBAm is stable underwater and improves the antifouling properties, as evidenced by the lower trans-membrane pressure required to retain targeted water fluxes than that required for the pristine membranes. The SBAm is also more effective than conventionally used sulfobetaine methacrylate (SBMA) for the zwitterion grafting on the surface to improve antifouling properties.

Authors: Amin Jafari, Nika Rajabian, Guojian Zhang, Mohamed Alaa Mohamed, Pedro Lei, Stelios T. Andreadis, Blaine A. Pfeifer, Chong Cheng

Year: 2020

Journal: Materials

Publisher: MDPI

Description: As a promising strategy for the treatment of various diseases, gene therapy has attracted increasing attention over the past decade. Among various gene delivery approaches, non-viral vectors made of synthetic biomaterials have shown significant potential. Due to their synthetic nature, non-viral vectors can have tunable structures and properties by using various building units. In particular, they can offer advantages over viral vectors with respect to biosafety and cytotoxicity. In this study, a well-defined poly(ethylene glycol)-block-poly(α-(propylthio-N,N-diethylethanamine hydrochloride)-ε-caprolactone) diblock polymer (PEG-b-CPCL) with one poly(ethylene glycol) (PEG) block and one tertiary amine-functionalized cationic poly(ε-caprolactone) (CPCL) block, as a novel non-viral vector in the delivery of plasmid DNA (pDNA), was synthesized and studied. Despite having a degradable polymeric structure, the polymer showed remarkable hydrolytic stability over multiple weeks. The optimal ratio of the polymer to pDNA for nanocomplex formation, pDNA release from the nanocomplex with the presence of heparin, and serum stability of the nanocomplex were probed through gel electrophoresis. Nanostructure of the nanocomplexes was characterized by DLS and TEM imaging. Relative to CPCL homopolymers, PEG-b-CPCL led to better solubility over a wide range of pH. Overall, this work demonstrates that PEG-b-CPCL possesses a range of valuable properties as a promising synthetic vector for pDNA delivery.

Authors: Amin Jafari

Year: 2020

Institution: The State University of New York at Buffalo, Department of Chemical and Biological Engineering

Description: Effective delivery of therapeutic agents, such as free drug molecules and genes, to specific biological sites presents a significant challenge for biomedical researchers. Several biological barriers are hindering the delivery of free therapeutic materials directly to the diseased tissue, such as degradation by serum protein absorption, macrophage internalization, sequestration in the reticuloendothelial system, clearance by the kidney, etc. Over the past decades, nanocarriers have emerged as promising biomaterials that may overcome biological barriers, protect the therapeutic cargo, and effectively deliver them to the diseased tissue. Polymer-based nanocarriers have drawn tremendous interest because of their significant potential to improve therapeutic biocompatibility, solubility, bioavailability, controlled release, and also minimizing therapeutic toxicity, and nonspecific interactions. With a thoughtful structural design …

Authors: Amin Jafari, Lingyue Yan, Mohamed Alaa Mohamed, Yun Wu, Chong Cheng

Year: 2020

Journal: Materials

Publisher: Multidisciplinary Digital Publishing Institute

Description: Nanoparticles have emerged as versatile carriers for various therapeutics and can potentially treat a wide range of diseases in an accurate and disease-specific manner. Polymeric biomaterials have gained tremendous attention over the past decades, owing to their tunable structure and properties. Aliphatic polyesters have appealing attributes, including biodegradability, non-toxicity, and the ability to incorporate functional groups within the polymer backbone. Such distinctive properties have rendered them as a class of highly promising biomaterials for various biomedical applications. In this article, well-defined alkyne-functionalized poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) diblock copolymer was synthesized and studied for pH-responsive delivery of doxorubicin (DOX). The alkyne-functionalized PEG-b-PCL diblock copolymer was prepared by the synthesis of an alkyne-functionalized ε-caprolactone (CL), followed by ring-opening polymerization (ROP) using PEG as the macroinitiator. The alkyne functionalities of PEG-b-PCL were modified through copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click reaction to graft aldehyde (ALD) groups and obtain PEG-b-PCL-g-ALD. Subsequently, DOX was conjugated on PEG-b-PCL-g-ALD through the Schiff base reaction. The resulting PEG-b-PCL-g-DOX polymer-drug conjugate (PDC) self-assembled into a nano-sized micellar structure with facilitated DOX release in acidic pH due to the pH-responsive linkage. The nanostructures of PDC micelles were characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS). In vitro studies of the PDC …

• Authors: Mohamed Alaa Mohamed, Afsoon Fallahi, Ahmed M.A. El-sokkary, Sahar Salehi, Magda A. Akl, Amin Jafari, Ali Tamayol, Hicham Fenniri, Ali Khademhosseini, Stelios T. Andreadis, Chong Cheng

• Year: 2019

• Journal: Progress in Polymer Science

• Description: Native tissues orchestrate their functions by complex interdependent cascades of biochemical and biophysical cues that vary spatially and temporally during cellular processes. Scaffolds with well-tuned structural, mechanical, and biochemical properties have been developed to guide cell behavior and provide insight on cell-matrix interaction. However, static scaffolds very often fail to mimic the dynamicity of native extracellular matrices. Stimuli-responsive scaffolds have emerged as powerful platforms that capture vital features of native tissues owing to their ability to change chemical and physical properties in response to cytocompatible stimuli, thus enabling on-demand manipulation of cell microenvironment. The vast expansion in biorthogonal chemistries and stimuli-responsive functionalities has fuelled further the development of new smart scaffolds that can permit multiple irreversible or reversible …

• Authors: Amin Jafari, Haotian Sun, Boyang Sun, Mohamed Alaa Mohamed, Honggang Cui, Chong Cheng

• Year: 2019

• Journal: Chemical Communications

• Publisher: Royal Society of Chemistry

• Description: Well-defined polyelectrolyte multilayer nanocapsules (NCs) are synthesized by layer-by-layer deposition of poly(acrylic acid) and poly(allylamine hydrochloride) over crystallized miniemulsion nanoparticles, followed by shell crosslinking and template removal. This synthetic approach allows well-controlled dimensions of NCs due to the high colloidal stability of the templates, and may also permit a broad composition range of NCs because of the mild conditions for template removal.

Authors: Amir Mokhtare, Amin Jafari, Edward P Furlani

Year: 2018

Journal: TechConnect Briefs

Publisher: TechConnect

Description: Unique interactions of ferrofluids with magnetic fields (MFs) can be exploited to achieve enhanced heat transfer for myriad fluidic based applications. In this study, we use numerical simulations to investigate the flow and heat transfer of a Fe3O4 ferrofluid in a vertical partially porous channel in the presence of a nonuniform (gradient) magnetic field provided by a permanent magnet. The flow is considered laminar and the Forchheimer–Brinkman extended Darcy model is used to predict flow through the porous region. The ferrofluid is heated as it flows upward in the vertical channel, mainly as it passes through the porous portion of the channel. The analysis shows that heat transfer enhancement for this system is predominantly due to three effects: the magnetic particles increase the effective thermal properties of the fluid, the porous medium provides a larger surface area that promotes heat transfer within the fluid and …

• Authors: Amin Jafari, Haotian Sun, Boyang Sun, Honggang Cui, Chong Cheng

• Year: 2019

• Conference: 257th ACS National Meeting & Exposition, Orlando, FL, United States, Mar. 31-Apr. 4

Authors: Amin Jafari, Guojian Zhang, Lingyue Yan, Mohamed Alaa Mohamed, Yun Wu, Blaine A. Pfeifer, Chong Cheng

Year: 2019

Conference: 257th ACS National Meeting & Exposition, Orlando, FL, United States, Mar. 31-Apr. 4, 2019