Page 25 - ASME_NEMB_2016_Program

TRACK 2 TRACK 2 Technical Program

de Estudios Avanzados Nanociencia, Madrid, Madrid,Spain, Jurgen -L >> 42% DPPC -L >> 16 % HSPC -L). Although DPPC has Tm above 37 °C,
Kosel, King Abdullah University of Science & Technology, Thuwal, they showed a remarkable liposome-serum precipitates in the media, de-
Select State/Province,Saudi Arabia, Aitziber Lopez Cortajarena, noting the importance of high Tm inclusion of HSPC in liposomal formulation.
Instituto Madrileno de Estudios Avanzados Nanociencia, Madrid, The in vitro cytotoxicity impact showed that DMPC- L and EPC -L were more
Madrid,Spain toxic than HSPC- L in C26 colon carcinoma, B16F0 melanoma, and NIH 3T3
fibrobalst cells, using MTT assay. Such toxicity could be related to increasing
drug release of these liposomes confirmed by exposing cells with culture
Cancer prevails as one of the most devastating diseases being at the top media containing liposomes at 37 °C within 3 h. Although fast delivering
of death causes for adults despite continuous development and innovation liposomes are more efficacious in eradicating cancerous cells, the toxic and
in cancer therapy. Nanotechnology may be used to achieve therapeutic serum-related aggregation may cause significant side effects in animals.
dosing, establish sustained-release drug profiles, and increase the half-life Interaction of liposomes with serum proteins is a matter of consideration as
of drugs avoiding efflux or degradation. In this context, magnetic nanowires these liposomes (EPC -L and DMPC -L) are more predisposed to become
(NWs) have shown a good biocompatibility and cellular internalization with a phagocytosed and accumulated in macrophages. As a result, there might be
low cytotoxic effect. In this study, we induced cancer cell death by combin- myelotoxicity and more hepatotoxicity as these liposomes might gathered
ing the chemotherapeutic effect of doxorubicin (DOXO)-functionalized iron more in these organs than those of Doxil®. These issues merit further investi-
NWs with mechanical disturbance under a low frequency alternating mag- gation in animal models.
netic field. Two different agents, APTES and BSA were separately used for
coating NWs permitting further functionalization with DOXO. Internalization
was qualitatively and quantitatively assessed for both formulations by confo-
cal reflection microscopy and inductively coupled plasma-mass spectrome- 2-4
try. From confocal reflection analysis, BSA formulations demonstrate to have NANOPARTICLES FOR IMMUNOENGINEERING
a higher internalization degree and a broader distribution within the cells,
as well as less agglomeration in comparison to APTES formulations. The
functionalized NWs generated a comparable cytotoxic effect in MDA-MB-231 Sam Houston 11:30am - 1:00pm
breast cancer cells in a DOXO concentration-dependent manner, (~60% at
the highest concentration tested) that was significantly different from the Session Organizer: Jonathan Lovell, University at Buffalo, Buffalo,
effect produced by the free DOXO (~95% at the same concentration) and NY, United States
non-functionalized NWs formulations (~10% at the same NWs concentration).
A synergistic cytotoxic effect is obtained when a low frequency magnetic 11:30am Harnessing Biomaterials to Study and Improve Thera-
field (1 mT, 10 Hz) is applied to cells treated with DOXO-functionalized BSA peutic Vaccines
or APTES-coated NWs that is again comparable (~70% at the highest con-
centration). Furthermore, the cytotoxic effect of both groups of coated NWs Keynote. NEMB2016-6156
in absence of the drug increased notoriously when the field is applied in an
NW concentration-dependent manner (~25% at the highest concentration Chris Jewell, University of Maryland, College Park, MD, United
tested). In summary, a combined method for cancer cell destruction was States
developed by the conjugation of the magneto-mechanical properties of the
iron NWs coupled with the chemotoxic effect of an anticancer drug. This Vaccines and immunotherapies have generated some of the largest impacts
combination yielded better results than the individual effects. Both APTES on human health in history, but a fundamental challenge facing the field is
and BSA coatings were efficient for the functionalization of the NWs and how to direct the specific properties of immune responses that are elicited.
demonstrated to be highly biocompatible.
This idea of tuning immune response is critical in designing more efficacious
and specific vaccines and immunotherapies. Toward this goal, we are devel-
10:40am In Vitro Characterization of Pegylated Liposomal oping two new strategies to study and exploit the interactions between bio-
Doxorubicin Containing Various Phosphatidylcholines with Dif- materials and lymph nodes – key tissues that coordinate adaptive immune
ferent Solid to Gel Phase Transition Temperatures response. In one approach we have combined direct lymph node injection
with degradable polymer depots. We are using this system to directly study
Technical Presentation. NEMB2016-6159 the link between local lymph node function and systemic immunity by prob-
ing the roles of signal density, combination, and material properties. We are
Hamidreza Farzaneh, Mashhad University of Medical Sciences, also applying this idea to directly reprogram the lymph node microenviron-
ment for therapeutic vaccination in the areas of autoimmunity and cancer. In
Mashhad, Iran mouse models of multiple sclerosis, depots loaded with regulatory cues and
self-antigens permanently reverse paralysis after a single treatment adminis-
The slow release of Pegylated liposomal doxorubicin (Doxil®) at tumor site tered at the peak of disease. These effects are systemic but antigen-specif-
might be an obstacle towards efficient cancerous tumor treatment. There- ic, and result from local changes in the lymph node microenvironment. The
fore, maybe modification of liposomes to lower solid-to-gel phase transition second focus area is the design of new modular materials we have created
temperature (Tm) increase drug efficacy. In this investigation, we prepared using polyionic immune signals to form stable vaccine capsules. These
four liposomal variants of Doxil® formulation, in which the main phospholip- immune polyelectrolyte multilayers (iPEMs) are self-assembled entirely from
id, Hydrogenated phosphatidylcholine (HSPC) were substituted with Egg antigens and adjuvants to allow selective activation of pro-inflammatory
derived PC, Dipalmitoeyl PC, and Dimeristoyl PC , termed HSPC -L, EPC signaling pathways without requiring other carrier components such as poly-
-L and DPPC -L and DMPC -L, respectively. The liposomes were prepared mers or lipids. In mice, peripheral injection of iPEMs enhances the function
by thin film hydration and ammonium sulphate gradient loading technique. of dendritic cells in draining lymph nodes, potently expands antigen-specific
The doxorubicin concentration and phospholipid content were determined T cells against the antigens used to build iPEMs, and provides protection
by respective spectrofluorimetry (Ex: 500; Em: 583) and according to Bart- during tumor challenge. Ultimately, these strategies could contribute to bet-
let phosphate method. The physicochemical properties of the liposomes, ter understanding of the interactions between biomaterials and the immune
including size distribution profile, drug to lipid ratio, and long-term drug re- system, and improve the rational design of materials that serve not only as
tention indicated that all liposomes are stable enough to retain similar drug carriers, but also as agents that actively direct immune response.
phospholipid ratios (1 mg doxorubicin/ 10 µmole phosphate), zeta average
and polydispersity indexes. The doxorubicin release follow-up in RPMI: FCS 12:00pm Biomimetic Nanovesicles for the Treatment of Inflam-
culture media (70:30 v/v) showed that liposomes did not release any drug
within 48 h. However, in long-term follow-ups, until one week, liposomes-se- matory-Based Diseases 25
rum protein aggregation occurred and the liposomes lost their drug con-
tents, correlated to the Tm of main phospholipid (74% DMPC -L >> 63% EPC Technical Presentation. NEMB2016-6048