Targeted and controlled drug delivery using a temperature and ultra-violet responsive liposome with excellent breast cancer suppressing ability

Abstract

Drug delivery systems (DDS) with favorable serum stability, high intra-tumor accumulation and tumor specific drug release are highly desired for promoting chemotherapeutic efficacy. However, a more stable DDS means it is more difficult to release its content, and vice versa. In order to resolve this conflict, a Fab conjugated thermo-responsive liposome (FCTRL) based on 1,2-bis(10,12-tricosadiynoyl)sn-glycero-3-phosphocholine (DC8,9PC) and P(IPPAm-co-DMAAm)-b-PLA diblock copolymer (PPDC) was developed in this study. DC8,9PC is a type of phospholipid, which can form intermolecular crosslinking within the liposomal bilayer by ultra-violet irradiation, contributing to superior serum stability in the blood vessels. PPDC is a thermo-responsive block copolymer, which demonstrates temperature controlled ON-OFF drug release with a volume phase transition temperature (VPTT) of approximately 38.5 C. The well modified FCTRLs are of the desired particle size, drug loading content and drug release profile. The surface morphology and pharmacokinetics were also characterized. The cellular uptake and intracellular accumulation of FCTRL are significantly promoted by its proper size, temperature regulated passive and Fab navigated active targeting. With the co-operation of all the above superiorities, the FCTRL DDS demonstrates exceptional excellent tumor suppression abilities against breast cancer in both in and ex vivo experiments, which merits further investigation in the clinic.

Ultrasonically controlled estrone-modified liposomes for estrogen-positive breast cancer therapy

“…An 11.2-fold increase in cellular uptake was achieved by the modification of a liposomal doxorubicin system with an SP5-2 moiety by Chang et al [21] Transferrinmodified nanoparticles demonstrated a six-fold increase in uptake versus control liposomes for a breast cancer cell line [22]. Similarly, several other actively targeted therapies have been developed to deal, specifically, with breast cancer using various targeting ligands including transferrin [23,24], estrogen [25], tamoxifen [26], folic acid [27], RGD peptide [28,29] and many others [30][31][32][33], yielding similar success to the previously outlined articles.…”

Rituximab (anti-CD20)-modified AZD-2014-encapsulated nanoparticles killing of B lymphoma cells

“…AZD-2014-loaded NPs and rituximab-conjugated NPs were prepared by use of a nanoprecipitation method [21]. PLGA-PEG or Ab-PLGA-PEG ($90 mg) and AZD-2014 (10 mg) were dissolved in 10 ml dimethyl sulfoxide, then slowly added dropwise with stirring at 2500 rpm to 30 ml deionized water for 30 min.…”

“…Considering that intravenous administration was planned, NP stability in serum should be known. For approximation of this value, we used Ab-NPs-AZD-2014 and NPs-AZD-2014 in 50% bovine serum albumin (BSA) in Dulbecco's modified Eagle Medium [21]. After incubation at 37 C for various times, size distribution NPs-albumin was measured with dynamic light scattering (DLS).…”

Novel reduction‐sensitive micellar nanoparticles assembled from Rituximab–doxorubicin conjugates as smart and intuitive drug delivery systems for the treatment of non‐Hodgkin's lymphoma

“…Several reasons may help explain the compromised clinical efficacy of ADCs: (i) premature deconjugation or degradation of ADCs in circulating blood due to linker instability; (ii) inadequate intracellular uptake by tumor cells due to rare target internalization of antibody–antigen complex; (iii) slow and deficient drug release inside tumor cells due to the gradual biodegradation behavior of linkers . However, it seems that more stable of an ADC product means more difficult to release its cytotoxicity agents inside tumor cells, and vice versa . The contradiction between linker stability and drug release remains a key point to resolve for enhanced tumor suppressing activities .…”

“…However, it seems that more stable of an ADC product means more difficult to release its cytotoxicity agents inside tumor cells, and vice versa . The contradiction between linker stability and drug release remains a key point to resolve for enhanced tumor suppressing activities . In addition, how to improve the tumor cell endocytosis of ADC products remains another important challenge …”