Liposomes for Cancer Theranostics

Abstract

Cancer is one of the most well-studied diseases and there have been significant advancements over the last few decades in understanding its molecular and cellular mechanisms. Although the current treatments (e.g., chemotherapy, radiotherapy, gene therapy and immunotherapy) have provided complete cancer remission for many patients, cancer still remains one of the most common causes of death in the world. The main reasons for the poor response rates for different cancers include the lack of drug specificity, drug resistance and toxic side effects (i.e., in healthy tissues). For addressing the limitations of conventional cancer treatments, nanotechnology has shown to be an important field for constructing different nanoparticles for destroying cancer cells. Due to their size (i.e., less than 1 μm), nanoparticles can deliver significant amounts of cancer drugs to tumors and are able to carry moieties (e.g., folate, peptides) for targeting specific types of cancer cells (i.e., through receptor-mediated endocytosis). Liposomes, composed of phospholipids and an interior aqueous core, can be used as specialized delivery vehicles as they can load different types of cancer therapy agents (e.g., drugs, photosensitizers, genetic material). In addition, the ability to load imaging agents (e.g., fluorophores, radioisotopes, MRI contrast media) enable these nanoparticles to be used for monitoring the progress of treatment. This review examines a wide variety of different liposomes for cancer theranostics, with the different available treatments (e.g., photothermal, photodynamic) and imaging modalities discussed for different cancers.

Keywords: image-guided therapy; imaging; nanoparticles; theranostics; therapy.

Figure 1

Ligand-targeted theranostic liposomes combining methylene blue attached upconversion nanoparticles for NIR-activated bioimaging and photodynamic therapy against HER-2 positive breast cancer. Illustration shows anti-HER2 peptide conjugated liposomes for selective bioimaging and PDT (i.e., using 975 nm NIR-laser) using two different combinations with LPs with free MB and UCNPs (a) and LPs with MB@UCNPs (b). Confocal images show that ROS can be generated in Group 3 LPs and Group 4 LPs using DCF-DA as a green fluorescent indicator after 5 min of laser excitation (i.e., at 975 nm) (c). Nuclei were counterstained with Hoechst shown in blue color. Scale represents: 50 μm. In vitro cell viability was determined using XTT assay to assess the SKBR-3 cell viability with different concentrations of LPs Groups (0–30 μM) and 975 nm NIR laser excitation for 5 min (d). Group 2 LPs represent LPs with UCNPs, Group 3 LPs represent LPs with free MB and UCNPs, and Group 4 LPs represent LPs with MB@UCNPs. Data are presented as mean ± SD (n = 3). Reprinted from Journal of Luminescence from [156], Copyright (2021), with permission from Elsevier.

Figure 2

Nanoliposomes co-encapsulating CT imaging contrast agent and photosensitizer for enhanced imaging-guided photodynamic therapy of cancer. (a) Schematic diagram illustrates nanoliposomes co-encapsulating CT imaging contrast agent (CTIA) and photosensitizer (PS). (b) Optical imaging was used for visualizing cellular internalization of TPPS₄ after 18 h incubation with free TPPS₄ (T), free iodixanol and TPPS₄ (IT), nanoliposomes encapsulating TPPS₄ (LT) or nanoliposomes co-encapsulating iodixanol and TPPS₄ (LIT). Images merging the transmission and fluorescence confocal channels are shown. Fluorescence of TPPS₄ (red pseudocolor) was excited by a 543 nm laser. (c) Survival of HeLa cells was determined one day post-PDT. The dark bars indicate 552 nm laser irradiation and the light ones indicate 640 nm laser irradiation at the same irradiation dose (15 J cm⁻²). (** p < 0.01 compared with T, IT and LT at the same laser irradiation dose). (d) Three-dimensional volume-rendered images were acquired from the nude mice bearing HeLa tumor xenografts after injection of free iodixanol or NLs with co-encapsulated iodixanol and TPPS₄ (LIT). Arrows indicate the location of the tumor. Reprinted with permission from Theranostics from [109]. Copyright (2019) Ivyspring International Publisher (distributed under Creative Commons Attribution (CC BY-NC) License at https://creativecommons.org/licenses/by-nc/4.0/ with no changes).

Figure 3

Verteporfin-loaded lipid-polymer liposomes for cancer theranostics. (a) Copolymer F127 modified with 5(6)-carboxyfluorescein and verteporfin can be loaded in liposomal system for cancer. (b) Absorption spectra of the vesicles are shown for DPPC/VP (red), F127-CF/DPPC (black) and F127-CF/DPPC/VP (blue). The insert shows the spectral overlap between the VP in methanol and in lipid-copolymer fluorescent liposomes. (c) The emission is shown as a function of the excitation wavelength. [DPPC] = 1.5 mmolL⁻¹; [F127] = 0.015% (w/V); [F127-CF] = 0.005% (w/V); [VP] = 1.0 μmolL⁻¹. (d) Cell viability of T98G cells was determined before and after the treatment with DPPC/F127-CF/VP. ([DPPC] = 1.5 mmolL⁻¹; [F127] = 0.015% w/V; [F127-CF] = 0.005% w/V; [VP] = 1.0 μmolL⁻¹). In PDT, the cell was irradiated for 20 min by a blue LED (5.52 mWcm⁻²). Incubation time = 2 h. Reprinted from Journal of Photochemistry and Photobiology B: Biology from [178], Copyright (2020), with permission from Elsevier.

Figure 4

Targeted theranostic DNA-biodot-based agents for imaging and treatment of non-small cell lung cancer. (a) The mechanism of targeted delivery of etoposide (ETP) and DNA biodots (DNA-BD) loaded, non-targeted and targeted (cetuximab-conjugated) theranostic liposomes in lung cancer imaging and therapy is shown. (b) Fluorescence microscopy images were taken using A-549 adenocarcinoma cells after 48 h incubation with free DNA-BD, BD-ETP-Liposomes, CTX-BD-ETP-Liposomes and cetuximab pretreated CTX-BD-ETP-Liposomes. (c) Levels of alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and Total Protein Count from female rats at day 0, day 7, day 14, day 30, after 7 day administration of normal saline, ETP (control), BD-ETP-Liposomes and CTX-BD-ETP-Liposomes were determined, (dose = 10 mg/kg), (n = 4). Reprinted from International Journal of Biological Macromolecules from [192], Copyright (2020), with permission from Elsevier.

Figure 5

Multifunctional gold liposomes as a theranostic platform for image-guided radiotherapy. (a) Gold nanoparticle-coated liposomes (i.e., Lipogold) as an all-in-one platform for cancer therapies. (b) Clonogenic survival of PC-3 cells was determined following photothermal therapy (PTT). (c) Dose survival curve was determined under different doses of 6 MV X-ray irradiation. N ≥ 5 with errors bars representing the standard deviation. * p < 0.05. Reprinted from International Journal of Pharmaceutics from [211], Copyright (2022), with permission from Elsevier.

Figure 6

Chemiluminescent liposomes for cancer theranostics under oxidative stress. (a) A schematic diagram of chemiluminescent liposomes composed of peroxyoxalate and curcumin. The liposomes generate light emission instantaneously in response to hydrogen peroxide. (b) Relative viability values of control cells and target cells were determined after treatment with curcumin-encapsulated peroxyoxalate liposomes at different concentrations for 24 h with cytotoxicity evaluations of hydrogen peroxide on cells after 1 day. Reported values are means ± SD for three independent determinations. (c) The dependence of the integral light emitted during PO-CL reaction in the cells is based on their amount in the sample (y = 935.47x + 231.02, R = 0.995). Reported values are means ± SD for three independent determinations. Reprinted from Analytica Chimica Acta from [217], Copyright (2019), with permission from Elsevier.