New Nanocarrier May Advance Treatment of Lung Damage in Pulmonary Fibrosis, Mouse Study Shows

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by Ana Pena, PhD |

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A new nanocarrier has been developed that is able to selectively deliver medicines to damaged cells in the lungs, alleviating fibrosis in mice, a study reports. 

Based on a naturally occurring process called cell senescence, the system also helps reduce the therapies’ toxic effects on healthy cells, and represents a promising technology for the treatment of conditions such as pulmonary fibrosis and cancer.

“This nano-carrier may pave the way for new therapeutic approaches for serious conditions, such as pulmonary fibrosis or to eliminate chemotherapy-induced senescent cells,” Manuel Serrano, PhD, senior author of the study and a Catalan Institution for Research and Advanced Studies researcher at the Institute for Research in Biomedicine in Barcelona, said in a press release.

The study, “A versatile drug delivery system targeting senescent cells,” was published in the journal EMBO Molecular Medicine.

Cell senescence is triggered by cell damage, in which cells cease to divide and proliferate but don’t die — these cells are often referred to as “zombie cells.” Upon persistent damage or aging, senescent cells may accumulate and lead to chronic inflammation and fibrosis.

In fact, senescent cells have been shown to contribute to multiple conditions including cancer and pulmonary fibrosis.

Nanocarriers are used to transport substances, such as medicines, within the body. In this case, the nanocarrier was developed based on a sugar molecule called galactose, which is preferentially taken up by damaged cells undergoing senescence. Taking advantage of this feature, researchers designed a drug encapsulating system composed of galactose-based molecules that selectively releases medicines into senescent cells.

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The effectiveness of the new nanocarriers in delivering medicines to tissues containing high concentrations of senescent cells was demonstrated in vitro and in two experimental mouse models, one of cancer and the other of pulmonary fibrosis.

In the mouse model of cancer and chemotherapy-induced senescence, the nanocarriers were seen to improve the delivery of doxorubicin — a cell-killing agent used in cancer treatment — to senescent tumor cells. In combination with the chemotherapy palbociclib (sold under the brand name Ibrance), this treatment increased tumor shrinking, compared with free doxorubicin plus palbociclib.

Moreover, the nanocarrier also improved the treatment of lung damage in mouse models of pulmonary fibrosis. In mice injected with doxorubicin-loaded nanocarriers, the therapy was preferentially released to senescing cells in the lung, killing them and, in turn, lowering collagen deposition and recovering breathing capacity, compared with untreated animals or those treated with doxorubicin alone.

One important advantage of this carrier is that it reduces the toxic side effects of therapies because it prevents their delivery to healthy, non-senescent cells.

Another potential application of the tool is to aid in diagnosis through clinical imaging, because the nanocarriers can transport fluorescent molecules that can be used to track damaged, senescent cells in the body.