Colloids and Surfaces B: Biointerfaces 162 (2018) 202–211
Contents lists available at ScienceDirect
Colloids and Surfaces B: Biointerfaces
journal homepage: www.elsevier.com/locate/colsurfb
Full length article
Photo-triggered destabilization of nanoscopic vehicles by
dihydroindolizine for enhanced anticancer drug delivery in cervical
carcinoma
Priya Singh
a
, Susobhan Choudhury
a
, Senthilguru Kulanthaivel
b
, Damayanti Bagchi
a
,
Indranil Banerjee
b
, Saleh A. Ahmed
c
, Samir Kumar Pal
a,∗
a
Department of Chemical, Biological & Macromolecular Sciences, S. N. Bose National Centre for Basic Sciences, Block JD, Sector III, Salt Lake, Kolkata 700
106, India
b
Department of Biotechnology and Medical Engineering, National Institute of Technology, Rourkela, Odisha 769008, India
c
Department of Chemistry, Faculty of Applied Sciences, Umm Al-Qura University, 21955 Makkah, Saudi Arabia
a r t i c l e i n f o
Article history:
Received 8 August 2017
Received in revised form 12 October 2017
Accepted 14 November 2017
Available online 15 November 2017
Keywords:
Controlled drug delivery
Nanoscopic vehicles
Photoinduced activation
Anticancer drug
Cervical cancer
a b s t r a c t
The efficacy and toxicity of drugs depend not only on their potency but also on their ability to reach
the target sites in preference to non-target sites. In this regards destabilization of delivery vehicles
induced by light can be an effective strategy for enhancing drug delivery with spatial and temporal
control. Herein we demonstrate that the photoinduced isomerization from closed (hydrophobic) to open
isomeric form (hydrophilic) of a novel DHI encapsulated in liposome leads to potential light-controlled
drug delivery vehicles. We have used steady state and picosecond resolved dynamics of a drug 8-anilino-
1-naphthalenesulfonic acid ammonium salt (ANS) incorporated in liposome to monitor the efficacy
of destabilization of liposome in absence and presence UVA irradiation. Steady state and picosecond
resolved polarization gated spectroscopy including the well-known strategy of solvation dynamics and
F¨ orster resonance energy transfer; reveal the possible mechanism out of various phenomena involved
in destabilization of liposome. We have also investigated the therapeutic efficacy of doxorubicin (DOX)
delivery from liposome to cervical cancer cell line HeLa. The FACS, confocal fluorescence microscopic and
MTT assay studies reveal an enhanced cellular uptake of DOX leading to significant reduction in cell via-
bility (∼40%) of HeLa followed by photoresponsive destabilization of liposome. Our studies successfully
demonstrate that these DHI encapsulated liposomes have potential application as a smart photosensitive
drug delivery system.
© 2017 Elsevier B.V. All rights reserved.
1. Introduction
Potential therapeutic (cargo drug) encapsulation coupled with
stimuli responsiveness of drug delivery systems (DDS) have gained
tremendous attention in recent years [1,2]. It not only eludes
the possibilities of premature drug release but also improves the
therapeutic efficacy by the means of enhanced spatio-temporal
accumulation of the therapeutic payload [3,4]. This further low-
ers the cytotoxic effect of the therapeutic drug other than the
tumor sites and also favors overcoming the drug resistance [5,6].
These classes of DDS are mostly composed of three ingredients
(i) a tumor targeting therapeutic carrier (ii) an external stimuli
∗
Corresponding author.
E-mail address: skpal@bose.res.in (S.K. Pal).
sensitive agents that can destabilize therapeutic carrier for effi-
cient drug delivery (iii) a drug capable for tracking the spatial
distribution, localization, and depletion from the DDS. Owing to
the encapsulation characteristics and biocompatibility, liposomes
recommend them as efficient carriers for therapeutic agents [7].
Out of the various published methods for triggering the release
of drug molecules from liposome, photoinduced destabilization is
a particularly attractive method for providing fast reaction rates
[8]. Photo induction or light triggering generally offers the great
benefit of not affecting physiological parameters such as tempera-
ture, pH and ionic strength, a fundamental requisite for biomedical
applications [9,10]. Liposome can be made photosensitive by using
photochromic agents that isomerize [11–14], polymerize [15–17],
fragment [18] or induce oxidative reactions [19,20] upon irradia-
tion [21,22].
https://doi.org/10.1016/j.colsurfb.2017.11.035
0927-7765/© 2017 Elsevier B.V. All rights reserved.