Fluence Rate-Dependent Kinetics of Light-Triggered Liposomal Doxorubicin Assessed by Quantitative Fluorescence-Based Endoscopic Probe

Abstract

Liposomal doxorubicin (Dox), a treatment option for recurrent ovarian cancer, often suffers from suboptimal biodistribution and efficacy, which might be addressed with precision drug delivery systems. Here, we introduce a catheter-based endoscopic probe designed for multispectral, quantitative monitoring of light-triggered drug release. This tool utilizes red-light photosensitive porphyrin-phospholipid (PoP), which is encapsulated in liposome bilayers to enhance targeted drug delivery. By integrating diffuse reflectance and fluorescence spectroscopy, our approach not only corrects for the effects of tissue optical properties but also ensures accurate drug delivery to deep-seated tumors. Preliminary results validate the probe's effectiveness in controlled settings, highlighting its potential for future clinical adaptation. This study sets the stage for in vivo applications, enabling the exploration of next-generation treatment paradigms for the management of cancer that involve optimizing chemotherapy administration for precision and control.

Keywords: diffuse fluorescence spectroscopy; diffuse reflectance spectroscopy; doxorubicin drug concentration; endoscopic probe; light-triggered release; photodynamic therapy; porphyrins.

Figure 1

Phantom calibration. (a) A schematic of the phantom optical properties (b) Raw Dox fluorescence counts show the effect of background optical property variation. Error bars represent the standard deviation between phantoms. (c) Corrected fluorescence shows a linear response to increasing Dox concentration and much less variation between phantoms. Error bars represent the standard deviation between phantoms.

Figure 2

The release kinetics. The time to complete release depends on the fluence rate. (a) Dox release as a function of time for different fluence rates. (b) Dox release as a function of fluence rate. (c) Pyro-fluorescence signal as a function of time. (d) Pyro-fluorescence signal as a function of fluence rate indicates the photobleaching of the porphyrin component.

Figure 3

(a) Background absorption differences showed different final values of raw fluorescence after release. (b) Corrected fluorescence fitting showed the same final Dox concentration after release for the two phantoms. (c) Pyro (PoP, HPPH) fluorescence showed a slight decrease throughout treatment. (d) The release in a mouse model.

Figure 4

Liposomal formulation of a “nano-balloon” for imaging and treatment. (a) PoP red (or Dox) fluorescence can be used to localize the cancer cell. NIR light triggers release of the drug (Doxorubicin-Dox) when Dox is in the middle of the “nano-balloon”. When NIR light activates the PoP (HPPH-porphyrin), it releases the Dox. (b) The combined fluorescence spectra from Dox and PoP indicate that fluorescence increases during the release, which allows for an image-guided drug-delivery approach.

Figure 5

Instrument setup. (a). Diagram of interstitial measurement and treatment system (b) Picture of the setup. (c) The picture of the interstitial needle probe. An 18-gauge needle is shown for size comparison. The inset shows the layout of the probe face.

Figure 6

Dox and PoP (Pyro) fluorescence quantification. (a) The basis spectra of autofluorescence (Auto), Doxorubicin (Dox), and PoP were used to quantify fluorescence concentrations. (b) A representative raw fluorescence signal measured pre- and post-Dox release.